Treatment of the underlying cause is required. Endotracheal intubation and mechanical ventilation are required in cases of severe respiratory failure (PaO2 less than 50 mmHg). Respiratory stimulants such as doxapram are rarely used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote (naloxone or flumazenil, respectively) will be given.

There is tentative evidence that in those with respiratory failure identified before arrival in hospital, continuous positive airway pressure can be useful when started before conveying to hospital.

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.

In people with stable OHS, the most important treatment is weight loss—by diet, through exercise, with medication, or sometimes weight loss surgery (bariatric surgery). This has been shown to improve the symptoms of OHS and resolution of the high carbon dioxide levels. Weight loss may take a long time and is not always successful. Bariatric surgery is avoided if possible, given the high rate of complications, but may be considered if other treatment modalities are ineffective in improving oxygen levels and symptoms. If the symptoms are significant, nighttime positive airway pressure (PAP) treatment is tried; this involves the use of a machine to assist with breathing. PAP exists in various forms, and the ideal strategy is uncertain. Some medications have been tried to stimulate breathing or correct underlying abnormalities; their benefit is again uncertain.

While many people with obesity hypoventilation syndrome are cared for on an outpatient basis, some deteriorate suddenly and when admitted to the hospital may show severe abnormalities such as markedly deranged blood acidity (pH<7.25) or depressed level of consciousness due to very high carbon dioxide levels. On occasions, admission to an intensive care unit with intubation and mechanical ventilation is necessary. Otherwise, "bi-level" positive airway pressure (see the next section) is commonly used to stabilize the patient, followed by conventional treatment.

Positive airway pressure, initially in the form of "continuous" positive airway pressure (CPAP), is a useful treatment for obesity hypoventilation syndrome, particularly when obstructive sleep apnea co-exists. CPAP requires the use during sleep of a machine that delivers a continuous positive pressure to the airways and preventing the collapse of soft tissues in the throat during breathing; it is administered through a mask on either the mouth and nose together or if that is not tolerated on the nose only (nasal CPAP). This relieves the features of obstructive sleep apnea and is often sufficient to remove the resultant accumulation of carbon dioxide. The pressure is increased until the obstructive symptoms (snoring and periods of apnea) have disappeared. CPAP alone is effective in more than 50% of people with OHS.

In some occasions, the oxygen levels are persistently too low (oxygen saturations below 90%). In that case, the hypoventilation itself may be improved by switching from CPAP treatment to an alternate device that delivers "bi-level" positive pressure: higher pressure during inspiration (breathing in) and a lower pressure during expiration (breathing out). If this too is ineffective in increasing oxygen levels, the addition of oxygen therapy may be necessary. As a last resort, tracheostomy may be necessary; this involves making a surgical opening in the trachea to bypass obesity-related airway obstruction in the neck. This may be combined with mechanical ventilation with an assisted breathing device through the opening.

As a side effect of medicines or recreational drugs, hypoventilation may become potentially life-threatening. Many different central nervous system (CNS) depressant drugs such as ethanol, benzodiazepines, barbiturates, GHB, sedatives and opioids produce respiratory depression when taken in large or excessive doses, or mixed with other depressants. Strong opiates (such as fentanyl, heroin, or morphine), barbiturates, and certain benzodiazepines (short acting ones and alprazolam) are known for depressing respiration. In an overdose, an individual may cease breathing entirely (go into respiratory arrest) which is rapidly fatal without treatment. Opioids, in overdose or combined with other depressants, are notorious for such fatalities.

In closed circuit SCUBA (rebreather) diving, exhaled carbon dioxide must be removed from the breathing system, usually by a scrubber containing a solid chemical compound with a high affinity for CO, such as soda lime. If not removed from the system, it may be re-inhaled, causing an increase in the inhaled concentration.

Acute respiratory distress syndrome is usually treated with mechanical ventilation in the intensive care unit (ICU). Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation (≥2 weeks) is necessary. The role of non-invasive ventilation is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with atypical pneumonias, lung bruising, or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate antibiotic therapy must be administered as soon as microbiological culture results are available, or clinical infection is suspected (whichever is earlier). Empirical therapy may be appropriate if local microbiological surveillance is efficient. The origin of infection, when surgically treatable, must be removed. When sepsis is diagnosed, appropriate local protocols should be enacted.

Inhaled nitric oxide (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS. Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity.

There is evidence to show that steroids given to babies less than 8 days old can prevent bronchopulmonary dysplasia. However, the risks of treatment may outweigh the benefits.

It is unclear if starting steroids more than 7 days after birth is harmful or beneficial. It is thus recommended that they only be used in those who cannot be taken off of a ventilator.

People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that biphasic cuirass ventilation can effectively be used without the need for a tracheotomy. Other potential treatments for Ondine's curse include oxygen therapy and medicine for stimulating the respiratory system. Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia.

Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is diaphragm pacing.

The hypercapnic state is routinely used to calibrate blood-oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI), a modality that is sensitive to changes in blood oxygenation. However, this calibration crucially relies on the assumption that hypercapnia has no effect on neuronal function, which is a matter of debate.

Individuals can benefit from a variety of physical therapy interventions. Persons with neurological/neuromuscular abnormalities may have breathing difficulties due to weak or paralyzed intercostal, abdominal and/or other muscles needed for ventilation. Some physical therapy interventions for this population include active assisted cough techniques, volume augmentation such as breath stacking, education about body position and ventilation patterns and movement strategies to facilitate breathing.

In those who are not palliative the primary treatment of shortness of breath is directed at its underlying cause. Extra oxygen is effective in those with hypoxia; however, this has no effect in those with normal blood oxygen saturations, even in those who are palliative.

Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide or both cannot be kept at normal levels. A drop in the oxygen carried in blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type I or Type II, based on whether there is a high carbon dioxide level. The definition of respiratory failure in clinical trials usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing.

The normal partial pressure reference values are: oxygen PaO more than , and carbon dioxide PaCO lesser than .

Administration of oxygen at 15 litres per minute by face mask or bag valve mask is often sufficient, but tracheal intubation with mechanical ventilation may be necessary. Suctioning of pulmonary oedema fluid should be balanced against the need for oxygenation. The target of ventilation is to achieve 92% to 96% arterial saturation and adequate chest rise. Positive end-expiratory pressure will generally improve oxygenation. Drug administration via peripheral veins is preferred over endotracheal administration. Hypotension remaining after oxygenation may be treated by rapid crystalloid infusion. Cardiac arrest in drowning usually presents as asystole or pulseless electrical activity. Ventricular fibrillation is more likely to be associated with complications of pre-existing coronary artery disease, severe hypothermia, or the use of epinephrine or norepinephrine.

Surfactant appears to improve outcomes when given to infants following meconium aspiration.

It has been recommended that the throat and nose of the baby be suctioned as soon as the head is delivered. However, this is not really useful and the revised Neonatal Resuscitation Guidelines no longer recommend it. When meconium staining of the amniotic fluid is present and the baby is born depressed, it is recommended that an individual trained in neonatal intubation use a laryngoscope and endotracheal tube to suction meconium from below the vocal cords. If the condition worsens, extracorporeal membrane oxygenation (ECMO) can be useful.

Albumin-lavage has not demonstrated to benefit outcomes of MAS. Steroid use has not demonstrated to benefit the outcomes of MAS.

MAS is difficult to prevent. Amnioinfusion, a method of thinning thick meconium that has passed into the amniotic fluid through pumping of sterile fluid into the amniotic fluid, has not shown a benefit.

The checks for responsiveness and breathing are carried out with the person horizontally supine. If unconscious but breathing, the recovery position is appropriate. If not breathing, rescue ventilation is necessary. Drowning can produce a gasping pattern of apnea while the heart is still beating, and ventilation alone may be sufficient, as the heart may be basically healthy, but hypoxic. The airway-breathing-circulation (ABC) sequence should be followed, rather than starting with compressions as is typical in cardiac arrest, as the basic problem is lack of oxygen. Five initial breaths are recommended, as the initial ventilation may be difficult because of water in the airways which can interfere with effective alveolar inflation. Thereafter a sequence of two breaths and 30 chest compressions is recommended, repeated until vital signs are re-established, the rescuers are unable to continue, or advanced life support is available.

Attempts to actively expel water from the airway by abdominal thrusts, Heimlich maneuver or positioning head downwards should be avoided as there is no obstruction by solids, and they delay the start of ventilation and increase the risk of vomiting, with a significantly increased risk of death, as aspiration of stomach contents is a common complication of resuscitation efforts.

Treatment for hypothermia may also be necessary. Because of the diving reflex, people submerged in cold water and apparently drowned may revive after a relatively long period of immersion. Rescuers retrieving a child from water significantly below body temperature should attempt resuscitation even after protracted immersion.

Preventing alveolar overdistension – Alveolar overdistension is mitigated by using small tidal volumes, maintaining a low plateau pressure, and most effectively by using volume-limited ventilation.

Preventing cyclic atelectasis (atelectotrauma) – Applied positive end-expiratory pressure (PEEP) is the principal method used to keep the alveoli open and lessen cyclic atelectasis.

Open lung ventilationn – Open lung ventilation is a ventilatory strategy that combines small tidal volumes (to lessen alveolar overdistension) and an applied PEEP above the low inflection point on the pressure-volume curve (to lessen cyclic atelectasis).

High frequency ventilation is thought to reduce ventilator-associated lung injury, especially in the context of ARDS and acute lung injury.

Permissive hypercapnia and hypoxaemia allow the patient to be ventilated at less aggressive settings and can thererfore mitigate all forms of ventilator associated lung injury

After a patient receives a diagnosis, the diagnosing physician can provide different options for treatment.

- Mechanical regulation of airflow and/or airway pressure:

- An experimental pacemaker for the diaphragm has shown promising results in overcoming central sleep apnea.

In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in "Pa"CO. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:

- Acute respiratory acidosis: HCO increases 1 mEq/L for each 10 mm Hg rise in "Pa"CO.

- Chronic respiratory acidosis: HCO rises 3.5 mEq/L for each 10 mm Hg rise in "Pa"CO.

The expected change in pH with respiratory acidosis can be estimated with the following equations:

- Acute respiratory acidosis: Change in pH = 0.008 X (40 − "Pa"CO)

- Chronic respiratory acidosis: Change in pH = 0.003 X (40 − "Pa"CO)

Respiratory acidosis does not have a great effect on electrolyte levels. Some small effects occur on calcium and potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Respiratory acidosis can be acute or chronic.

- In "acute respiratory acidosis", the "Pa"CO is elevated above the upper limit of the reference range (over 6.3 kPa or 45 mm Hg) with an accompanying acidemia (pH <7.36).

- In "chronic respiratory acidosis", the "Pa"CO is elevated above the upper limit of the reference range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO >30 mm Hg).

There is limited evidence for medication but acetazolamide "may be considered" for the treatment of central sleep apnea; it also found that zolpidem and triazolam may be considered for the treatment of central sleep apnea, but "only if the patient does not have underlying risk factors for respiratory depression". Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.

VALI does not need to be distinguished from progressive ALI/ARDS because management is the same in both. Additionally, definitive diagnosis of VALI may not be possible because of lack of sign or symptoms.

The rate of BPD varies among institutions, which may reflect neonatal risk factors, care practices (e.g., target levels for acceptable oxygen saturation), and differences in the clinical definitions of BPD.