The symptoms of generalized hypoxia depend on its severity and acceleration of onset.

In the case of altitude sickness, where hypoxia develops gradually, the symptoms include fatigue, numbness / tingling of extremities, nausea, and anoxia. In severe hypoxia, or hypoxia of very rapid onset, ataxia, confusion / disorientation / hallucinations / behavioral change, severe headaches / reduced level of consciousness, papilloedema, breathlessness, pallor, tachycardia, and pulmonary hypertension eventually leading to the late signs cyanosis, slow heart rate / cor pulmonale, and low blood pressure followed by death.

Because hemoglobin is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red color that it has when bound to oxygen (oxyhemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye. In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic. Hypoxia can cause premature birth, and injure the liver, among other deleterious effects.

If tissue is not being perfused properly, it may feel cold and appear pale; if severe, hypoxia can result in cyanosis, a blue discoloration of the skin. If hypoxia is very severe, a tissue may eventually become gangrenous.

Extreme pain may also be felt at or around the site.

In an acute context, hypoxemia can cause symptoms such as those in respiratory distress. These include breathlessness, an increased rate of breathing, use of the chest and abdominal muscles to breathe, and lip pursing.

Chronic hypoxemia may be compensated or uncompensated. The compensation may cause symptoms to be overlooked initially, however, further disease or a stress such as any increase in oxygen demand may finally unmask the existing hypoxemia. In a compensated state, blood vessels supplying less-ventilated areas of the lung may selectively contract, to redirect the blood to areas of the lungs which are better ventilated. However, in a chronic context, and if the lungs are not well ventilated generally, this mechanism can result in pulmonary hypertension, overloading the right ventricle of the heart and causing cor pulmonale and right sided heart failure. Polycythemia can also occur. In children, chronic hypoxemia may manifest as delayed growth, neurological development and motor development and decreased sleep quality with frequent sleep arousals.

Other symptoms of hypoxemia may include cyanosis, digital clubbing, and symptoms that may relate to the cause of the hypoxemia, including cough and hemoptysis.

Serious hypoxemia occurs (1) when the partial pressure of oxygen in blood is less than 60 mm Hg, (the beginning of the steep portion of the oxygen–haemoglobin dissociation curve, where a small decrease in the partial pressure of oxygen results in a large decrease in the oxygen content of the blood); or (2) when hemoglobin oxygen saturation is less than 90%. Severe hypoxia can lead to respiratory failure

"Hypoxemia" refers to low oxygen in the blood, and the more general term "hypoxia" is an abnormally low oxygen content in any tissue or organ, or the body as a whole. Hypoxemia can cause hypoxia (hypoxemic hypoxia), but hypoxia can also occur via other mechanisms, such as anemia.

Hypoxemia is usually defined in terms of reduced partial pressure of oxygen (mm Hg) in arterial blood, but also in terms of reduced content of oxygen (ml oxygen per dl blood) or percentage saturation of hemoglobin (the oxygen binding protein within red blood cells) with oxygen, which is either found singly or in combination.

While there is general agreement that an arterial blood gas measurement which shows that the partial pressure of oxygen is lower than normal constitutes hypoxemia, there is less agreement concerning whether the oxygen content of blood is relevant in determining hypoxemia. This definition would include oxygen carried by hemoglobin. The oxygen content of blood is thus sometimes viewed as a measure of tissue delivery rather than hypoxemia.

Just as extreme hypoxia can be called anoxia, extreme hypoxemia can be called anoxemia.

Hypoxic hypoxia is a result of insufficient oxygen available to the lungs. A blocked airway, a drowning or a reduction in partial pressure (high altitude above 10,000 feet) are examples of how lungs can be deprived of oxygen. Some medical examples are abnormal pulmonary function or respiratory obstruction. Hypoxic hypoxia is seen in patients suffering from chronic obstructive pulmonary diseases (COPD), neuromuscular diseases or interstitial lung disease.

Disorders like congenital central hypoventilation syndrome (CCHS) and ROHHAD (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, with autonomic dysregulation) are recognized as conditions that are associated with hypoventilation. CCHS may be a significant factor in some cases of sudden infant death syndrome (SIDS), often termed "cot death" or "crib death".

The opposite condition is hyperventilation (too much ventilation), resulting in low carbon dioxide levels (hypocapnia), rather than hypercapnia.

Cyanosis is defined as a bluish discoloration, especially of the skin and mucous membranes, due to excessive concentration of deoxyhemoglobin in the blood caused by deoxygenation.

Cyanosis is divided into two main types: Central (around the core, lips, and tongue) and Peripheral (only the extremities or fingers).

The brain requires approximately 3.3 ml of oxygen per 100 g of brain tissue per minute. Initially the body responds to lowered blood oxygen by redirecting blood to the brain and increasing cerebral blood flow. Blood flow may increase up to twice the normal flow but no more. If the increased blood flow is sufficient to supply the brain's oxygen needs then no symptoms will result.

However, if blood flow cannot be increased or if doubled blood flow does not correct the problem, symptoms of cerebral hypoxia will begin to appear. Mild symptoms include difficulties with complex learning tasks and reductions in short-term memory. If oxygen deprivation continues, cognitive disturbances, and decreased motor control will result. The skin may also appear bluish (cyanosis) and heart rate increases. Continued oxygen deprivation results in fainting, long-term loss of consciousness, coma, seizures, cessation of brain stem reflexes, and brain death.

Objective measurements of the severity of cerebral hypoxia depend on the cause. Blood oxygen saturation may be used for hypoxic hypoxia, but is generally meaningless in other forms of hypoxia. In hypoxic hypoxia 95–100% saturation is considered normal; 91–94% is considered mild and 86–90% moderate. Anything below 86% is considered severe.

It should be noted that cerebral hypoxia refers to oxygen levels in brain tissue, not blood. Blood oxygenation will usually appear normal in cases of hypemic, ischemic, and hystoxic cerebral hypoxia. Even in hypoxic hypoxia blood measures are only an approximate guide; the oxygen level in the brain tissue will depend on how the body deals with the reduced oxygen content of the blood.

Central cyanosis is often due to a circulatory or ventilatory problem that leads to poor blood oxygenation in the lungs. It develops when arterial oxygen saturation drops to ≤85% or ≤75%.

Acute cyanosis can be as a result of asphyxiation or choking, and is one of the definite signs that respiration is being blocked.

Central cyanosis may be due to the following causes:

1. Central nervous system (impairing normal ventilation):

- Intracranial hemorrhage

- Drug overdose (e.g. heroin)

- Tonic–clonic seizure (e.g. grand mal seizure)

2. Respiratory system:

- Pneumonia

- Bronchiolitis

- Bronchospasm (e.g. asthma)

- Pulmonary hypertension

- Pulmonary embolism

- Hypoventilation

- Chronic obstructive pulmonary disease, or COPD (emphysema)

3. Cardiovascular diseases:

- Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels)

- Heart failure

- Valvular heart disease

- Myocardial infarction

4. Blood:

- Methemoglobinemia * Note this causes "spurious" cyanosis, in that, since methemoglobin appears blue, the patient can appear cyanosed even in the presence of a normal arterial oxygen level.

- Polycythaemia

- Congenital cyanosis (HbM Boston) arises from a mutation in the α-codon which results in a change of primary sequence, H → Y. Tyrosine stabilises the Fe(III) form (oxyhaemoglobin) creating a permanent T-state of Hb.

5. Others:

- High altitude, cyanosis may develop in ascents to altitudes >2400 m.

- Hypothermia

- Obstructive sleep apnea

The main manifestations of carbon monoxide poisoning develop in the organ systems most dependent on oxygen use, the central nervous system and the heart. The initial symptoms of acute carbon monoxide poisoning include headache, nausea, malaise, and fatigue. These symptoms are often mistaken for a virus such as influenza or other illnesses such as food poisoning or gastroenteritis. Headache is the most common symptom of acute carbon monoxide poisoning; it is often described as dull, frontal, and continuous. Increasing exposure produces cardiac abnormalities including fast heart rate, low blood pressure, and cardiac arrhythmia; central nervous system symptoms include delirium, hallucinations, dizziness, unsteady gait, confusion, seizures, central nervous system depression, unconsciousness, respiratory arrest, and death. Less common symptoms of acute carbon monoxide poisoning include myocardial ischemia, atrial fibrillation, pneumonia, pulmonary edema, high blood sugar, lactic acidosis, muscle necrosis, acute kidney failure, skin lesions, and visual and auditory problems.

One of the major concerns following acute carbon monoxide poisoning is the severe delayed neurological manifestations that may occur. Problems may include difficulty with higher intellectual functions, short-term memory loss, dementia, amnesia, psychosis, irritability, a strange gait, speech disturbances, Parkinson's disease-like syndromes, cortical blindness, and a depressed mood. Depression may occur in those who did not have pre-existing depression. These delayed neurological sequelae may occur in up to 50% of poisoned people after 2 to 40 days. It is difficult to predict who will develop delayed sequelae; however, advanced age, loss of consciousness while poisoned, and initial neurological abnormalities may increase the chance of developing delayed symptoms.

One classic sign of carbon monoxide poisoning is more often seen in the dead rather than the living – people have been described as looking red-cheeked and healthy (see below). However, since this "cherry-red" appearance is common only in the deceased, and is unusual in living people, it is not considered a useful diagnostic sign in clinical medicine. In pathological (autopsy) examination the ruddy appearance of carbon monoxide poisoning is notable because unembalmed dead persons are normally bluish and pale, whereas dead carbon-monoxide poisoned persons may simply appear unusually lifelike in coloration. The colorant effect of carbon monoxide in such postmortem circumstances is thus analogous to its use as a red colorant in the commercial meat-packing industry.

Cerebral hypoxia is typically grouped into four categories depending on the severity and location of the brain's oxygen deprivation:

1. Diffuse cerebral hypoxia – A mild to moderate impairment of brain function due to low oxygen levels in the blood.

2. Focal cerebral ischemia – A stroke occurring in a localized area that can either be acute or transient. This may be due to a variety of medical conditions such as an aneurysm that causes a hemorrhagic stroke, or an occlusion occurring in the affected blood vessels due to a thrombus (thrombotic stroke) or embolus (embolic stroke). Focal cerebral ischemia constitutes a large majority of the clinical cases in stroke pathology with the infarct usually occurring in the middle cerebral artery (MCA).

3. Global cerebral ischemia – A complete stoppage of blood flow to the brain.

4. Cerebral infarction – A "stroke", caused by complete oxygen deprivation due to an interference in cerebral blood flow which affects multiple areas of the brain.

Cerebral hypoxia can also be classified by the cause of the reduced brain oxygen:

- Hypoxic hypoxia – Limited oxygen in the environment causes reduced brain function. Divers, aviators, mountain climbers, and fire fighters are all at risk for this kind of cerebral hypoxia. The term also includes oxygen deprivation due to obstructions in the lungs. Choking, strangulation, the crushing of the windpipe all cause this sort of hypoxia. Severe asthmatics may also experience symptoms of hypoxic hypoxia.

- Hypemic hypoxia – Reduced brain function is caused by inadequate oxygen in the blood despite adequate environmental oxygen. Anemia and carbon monoxide poisoning are common causes of hypemic hypoxia.

- Ischemic hypoxia ( or "stagnant hypoxia") – Reduced brain oxygen is caused by inadequate blood flow to the brain. Stroke, shock, cardiac arrest and heart attack may cause stagnant hypoxia. Ischemic hypoxia can also be created by pressure on the brain. Cerebral edema, brain hemorrhages and hydrocephalus exert pressure on brain tissue and impede their absorption of oxygen.

- Histotoxic hypoxia – Oxygen is present in brain tissue but cannot be metabolized by the brain tissue. Cyanide poisoning is a well-known example.

Inert gas asphyxiation is a form of asphyxiation which results from breathing a physiologically inert gas in the absence of oxygen, or a low amount of oxygen, rather than atmospheric air (which is largely composed of nitrogen and oxygen). Examples of physiologically inert gases, which have caused accidental or deliberate death by this mechanism, are: argon, helium, nitrogen and methane. The term "physiologically inert" is used to indicate a gas which has no toxic or anesthetic properties and does not act upon the heart or hemoglobin. Instead, the gas acts as a simple diluent to reduce oxygen concentration in inspired gas and blood to dangerously low levels, thereby eventually depriving all cells in the body of oxygen.

According to the U.S. Chemical Safety and Hazard Investigation Board, in humans, "breathing an oxygen deficient atmosphere can have serious and immediate effects, including unconsciousness after only one or two breaths. The exposed person has no warning and cannot sense that the oxygen level is too low." In the US, at least 80 people died due to accidental nitrogen asphyxiation between 1992 and 2002. Hazards with inert gases and the risks of asphyxiation are well established.

An occasional cause of accidental death in humans, inert gas asphyxia with gases including helium, nitrogen, methane, and argon, has been used as a suicide method. Inert gas asphyxia has been advocated by proponents of euthanasia, using a gas-retaining plastic hood device colloquially referred to as a suicide bag.

Nitrogen asphyxiation has been suggested by a number of lawmakers and other advocates as a more humane way to carry out capital punishment. In April 2015, the Oklahoma Governor Mary Fallin signed a bill authorizing nitrogen asphyxiation as an alternative execution method in cases where the state's preferred method of lethal injection was not available as an option.

Chronic exposure to relatively low levels of carbon monoxide may cause persistent headaches, lightheadedness, depression, confusion, memory loss, nausea and vomiting. It is unknown whether low-level chronic exposure may cause permanent neurological damage. Typically, upon removal from exposure to carbon monoxide, symptoms usually resolve themselves, unless there has been an episode of severe acute poisoning. However, one case noted permanent memory loss and learning problems after a 3-year exposure to relatively low levels of carbon monoxide from a faulty furnace. Chronic exposure may worsen cardiovascular symptoms in some people. Chronic carbon monoxide exposure might increase the risk of developing atherosclerosis. Long-term exposures to carbon monoxide present the greatest risk to persons with coronary heart disease and in females who are pregnant.

Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects.

If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants. However an opioid antagonist may also precipitate an opioid withdrawal syndrome in chronic users.

People have different susceptibilities to altitude sickness; for some otherwise healthy people, acute altitude sickness can begin to appear at around above sea level, such as at many mountain ski resorts, equivalent to a pressure of . This is the most frequent type of altitude sickness encountered. Symptoms often manifest themselves six to ten hours after ascent and generally subside in one to two days, but they occasionally develop into the more serious conditions. Symptoms include headache, fatigue, stomach illness, dizziness, and sleep disturbance. Exertion aggravates the symptoms.

Those individuals with the lowest initial partial pressure of end-tidal pCO (the lowest concentration of carbon dioxide at the end of the respiratory cycle, a measure of a higher alveolar ventilation) and corresponding high oxygen saturation levels tend to have a lower incidence of acute mountain sickness than those with high end-tidal pCO and low oxygen saturation levels.

When humans breathe in an asphyxiant gas, such as pure nitrogen, helium, neon, argon, sulfur hexafluoride, methane, or any other physiologically inert gas(es), they exhale carbon dioxide without re-supplying oxygen. Physiologically inert gases (those that have no toxic effect, but merely dilute oxygen) are generally free of odor and taste. As such, the human subject detects little abnormal sensation as the oxygen level falls. This leads to asphyxiation (death from lack of oxygen) without the painful and traumatic feeling of suffocation (the hypercapnic alarm response, which in humans arises mostly from carbon dioxide levels rising), or the side effects of poisoning. In scuba diving rebreather accidents, there is often little sensation but euphoria—however, a slow decrease in oxygen breathing gas content has effects which are quite variable. By contrast, suddenly breathing pure inert gas causes oxygen levels in the blood to fall precipitously, and may lead to unconsciousness in only a few breaths, with no symptoms at all.

Some animal species are better equipped than humans to detect hypoxia, and these species are more uncomfortable in low-oxygen environments that result from inert gas exposure.

Headaches are the primary symptom used to diagnose altitude sickness, although a headache is also a symptom of dehydration. A headache occurring at an altitude above a pressure of combined with any one or more of the following symptoms, may indicate altitude sickness:

Early symptoms of high-altitude cerebral edema (HACE) generally correspond with those of moderate to severe acute mountain sickness (AMS). Initial symptoms of HACE commonly include confusion, loss of consciousness, fever, ataxia, photophobia, rapid heart beat, lassitude, and an altered mental state. Sufferers generally attempt to cease physical activities, regardless of their necessity for survival. Severe headaches develop and sufferers lose the ability to sit up. Retinal venous dilation occurs in 59% of people with HACE. Rarer symptoms include brisk deep tendon reflexes, retinal hemorrhages, blurred vision, extension plantar reflexes, and ocular paralysis. Cranial nerve palsies occur in some unusual cases.

In the bestselling 1996 non-fiction book "Into Thin Air: A Personal Account of the Mt. Everest Disaster", Jon Krakauer describes the effects of HACE upon Dale Kruse, a forty-four-year-old dentist and one of the members of Scott Fischer's team:

‘Kruse was having an incredibly difficult time simply trying to dress himself. He put his climbing harness on inside out, threaded it through the fly of his wind suit, and failed to fasten the buckle; fortunately, Fisher and Neal Beidleman noticed the screwup before Kruse started to descend. "If he'd tried to rappel down the ropes like that," says Beidleman, "he would have immediately popped out of his harness and fallen to the bottom of the Lhotse Face."

‘"It was like I was very drunk," Kruse recollects. "I couldn't walk without stumbling, and completely lost the ability to think or speak. It was a really strange feeling. I'd have some word in my mind, but I couldn't figure out how to bring it to my lips. So Scott and Neal had to get me dressed and make sure my harness was on correctly, then Scott lowered me down the fixed ropes." By the time Kruse arrived in Base Camp, he says, "it was still another three or four days before I could walk from my tent to the mess tent without stumbling all over the place."’

Patients with HACE have an elevated white blood cell count, but otherwise their blood count and biochemistry are normal. If a lumbar puncture is performed, it will show normal cerebral spinal fluid and cell counts but an increase in pressure. In one study, CT scans of patients with HACE exhibited ventricle compression and low density in the cerebellum. Only a few autopsies have been performed on fatal cases of HACE; they showed swollen gyri, spongiosis of white matter, and compressed sulci. There was some variation between individuals, and the results may not be typical of HACE deaths.

Apnea of prematurity can be readily identified from other forms of infant apnea such as obstructive apnea, hypoventilation syndromes, breathing regulation issues during feeding, and reflux associated apnea with an infant pneumogram or infant apnea/sleep study.

Apnea of prematurity is defined as cessation of breathing by a premature infant that lasts for more than 20 seconds and/or is accompanied by hypoxia or bradycardia. Apnea is traditionally classified as either "obstructive, central, or mixed". Obstructive apnea may occur when the infant's neck is hyperflexed or conversely, hyperextended. It may also occur due to low pharyngeal muscle tone or to inflammation of the soft tissues, which can block the flow of air though the pharynx and vocal cords. Central apnea occurs when there is a lack of respiratory effort. This may result from central nervous system immaturity, or from the effects of medications or illness. Many episodes of apnea of prematurity may start as either obstructive or central, but then involve elements of both, becoming mixed in nature.

Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. Intrauterine growth restriction (IUGR) may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, ADHD, eating disorders and cerebral palsy.

Physiological and symptomatic changes often vary according to the altitude involved.

The Lake Louise Consensus Definition for High-Altitude Pulmonary Edema has set widely used criteria for defining HAPE symptoms:

Symptoms: at least two of:

- Difficulty in breathing (dyspnea) at rest

- Cough

- Weakness or decreased exercise performance

- Chest tightness or congestion

Signs: at least two of:

- Crackles or wheezing (while breathing) in at least one lung field

- Central cyanosis (blue skin color)

- Tachypnea (rapid shallow breathing)

- Tachycardia (rapid heart rate)

The initial cause of HAPE is a shortage of oxygen caused by the lower air pressure at high altitudes.

The mechanisms by which this oxygen shortage causes HAPE are poorly understood, but two processes are believed to be important:

1. Increased pulmonary arterial and capillary pressures (pulmonary hypertension) secondary to hypoxic pulmonary vasoconstriction.

2. An idiopathic non-inflammatory increase in the permeability of the vascular endothelium.

Although higher pulmonary arterial pressures are associated with the development of HAPE, the presence of pulmonary hypertension may not in itself be sufficient to explain the development of edema: severe pulmonary hypertension can exist in the absence of clinical HAPE in subjects at high altitude.

The World Health Organization in 2005 defined drowning as "the process of experiencing respiratory impairment from submersion/immersion in liquid". This definition does not imply death, or even the necessity for medical treatment after removal of the cause, nor that any fluid enters the lungs. The WHO further recommended that outcomes should be classified as: death, morbidity, and no morbidity. There was also consensus that the terms wet, dry, active, passive, silent, and secondary drowning should no longer be used.

Experts differentiate between distress and drowning.

- Distress – people "in trouble", but who still have the ability to keep afloat, signal for help and take actions.

- Drowning – people "suffocating" and in "imminent danger of death within seconds".

Generally, high-altitude pulmonary edema (HAPE) or AMS precede HACE. In patients with AMS, the onset of HACE is usually indicated by vomiting, headache that does not respond to non-steroidal anti-inflammatory drugs, hallucinations, and stupor. In some situations, however, AMS progresses to HACE without these symptoms. HACE must be distinguished from conditions with similar symptoms, including stroke, intoxication, psychosis, diabetic symptoms, meningitis, or ingestion of toxic substances. It should be the first diagnosis ruled out when sickness occurs while ascending to a high altitude.

HACE is generally preventable by ascending gradually with frequent rest days while climbing or trekking. Not ascending more than daily and not sleeping at a greater height than more than the previous night is recommended. The risk of developing HACE is diminished if acetazolamide or dexamethasone are administered. Generally, the use of acetazolamide is preferred, but dexamethasone can be used for prevention if there are side effects or contraindications. Some individuals are more susceptible to HACE than others, and physical fitness is not preventative. Age and sex do not by themselves affect vulnerability to HACE.

There are various causes for intrauterine hypoxia (IH). The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia. While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium (GOPEC) in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia.

Nicotine alone has been shown to be a teratogen which affects the autonomic nervous system, leading to increased susceptibility to hypoxia-induced brain damage.

Maternal anemia in which smoking has also been implicated is another factor associated with IH/BA. Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells (NRBC), thereby reducing the amount of red blood cells available for oxygen transport.

The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of hypoxic ischemic encephalopathy.