The most common cause is viral infection and includes adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus. It can also be caused by Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or HIV. The second most common cause is bacterial infection of which the predominant is Group A β-hemolytic streptococcus (GABHS), which causes strep throat. Less common bacterial causes include: "Staphylococcus aureus" (including methicillin resistant Staphylococcus aureus or MRSA ),"Streptococcus pneumoniae", "Mycoplasma pneumoniae", "Chlamydia pneumoniae", "Bordetella pertussis", "Fusobacterium" sp., "Corynebacterium diphtheriae", "Treponema pallidum", and "Neisseria gonorrhoeae".

Anaerobic bacteria have been implicated in tonsillitis and a possible role in the acute inflammatory process is supported by several clinical and scientific observations.

Under normal circumstances, as viruses and bacteria enter the body through the nose and mouth, they are filtered in the tonsils. Within the tonsils, white blood cells of the immune system destroy the viruses or bacteria by producing inflammatory cytokines like phospholipase A2, which also lead to fever. The infection may also be present in the throat and surrounding areas, causing inflammation of the pharynx.

Sometimes, tonsillitis is caused by an infection of spirochaeta and treponema, in this case called Vincent's angina or Plaut-Vincent angina.

Some cases of pharyngitis are caused by fungal infection such as Candida albicans causing oral thrush.

Pharyngitis may also be caused by mechanical, chemical or thermal irritation, for example cold air or acid reflux. Some medications may produce pharyngitis such as pramipexole and antipsychotics.

Viruses that may cause adenoiditis include adenovirus, rhinovirus and paramyxovirus. Bacterial causes include Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and various species of Staphylococcus including Staphylococcus aureus.

Since the advent of penicillin in the 1940s, a major preoccupation in the treatment of streptococcal tonsillitis has been the prevention of rheumatic fever, and its major effects on the nervous system (Sydenham's chorea) and heart. Recent evidence would suggest that the rheumatogenic strains of group A beta hemolytic strep have become markedly less prevalent and are now only present in small pockets such as in Salt Lake City, USA. This brings into question the rationale for treating tonsillitis as a means of preventing rheumatic fever.

Complications may rarely include dehydration and kidney failure due to difficulty swallowing, blocked airways due to inflammation, and pharyngitis due to the spread of infection.

An abscess may develop lateral to the tonsil during an infection, typically several days after the onset of tonsillitis. This is termed a peritonsillar abscess (or quinsy).

Rarely, the infection may spread beyond the tonsil resulting in inflammation and infection of the internal jugular vein giving rise to a spreading septicaemia infection (Lemierre's syndrome).

In chronic/recurrent cases (generally defined as seven episodes of tonsillitis in the preceding year, five episodes in each of the preceding two years or three episodes in each of the preceding three years), or in acute cases where the palatine tonsils become so swollen that swallowing is impaired, a tonsillectomy can be performed to remove the tonsils. Patients whose tonsils have been removed are still protected from infection by the rest of their immune system.

In strep throat, very rarely diseases like rheumatic fever or glomerulonephritis can occur. These complications are extremely rare in developed nations but remain a significant problem in poorer nations. Tonsillitis associated with strep throat, if untreated, is hypothesized to lead to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

It is currently believed that bacterial biofilms play an integral role in the harboring of chronic infection by tonsil and adenoid tissue so contributing to recurrent sinusitis and recurrent or persistent ear disease. Also, enlarged adenoids and tonsils may lead to the obstruction of the breathing patterns in children, causing apnea during sleep.

The most common bacteria isolated are Haemophilus influenzae, group A beta-hemolytic Streptococcus, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniea. Heamophilus influenza, Moraxella catarrhalis and Streptococcus pneumonia are the three most resistant pathogens of otitis and rhinosinisitis in children suffering from these diseases.

It is a commonly encountered otorhinolaryngological (ENT) emergency.

The number of new cases per year of peritonsillar abscess in the United States has been estimated approximately at 30 cases per 100,000 people. In a study in Northern Ireland, the number of new cases was 10 cases per 100,000 people per year.

In Denmark, the new number of new cases is higher and reaches 41 cases per 100,000 people per year. Younger children who develop a peritonsillar abscess are often immunocompromised and in them, the infection can cause airway obstruction.

PTA usually arises as a complication of an untreated or partially treated episode of acute tonsillitis. The infection, in these cases, spreads to the peritonsillar area (peritonsillitis). This region comprises loose connective tissue and is hence susceptible to formation of an abscess. PTA can also occur "". Both aerobic and anaerobic bacteria can be causative. Commonly involved aerobic pathogens include "Streptococcus, Staphylococcus" and "Haemophilus". The most common anaerobic species include "Fusobacterium necrophorum", " Peptostreptococcus", "Prevotella species", and "Bacteroides".

Typically spreads via the fecal-oral route or via respiratory droplets.

Herpangina, also called mouth blisters, is a painful mouth infection caused by coxsackieviruses. Usually, herpangina is produced by one particular strain of coxsackie virus A (and the term "herpangina virus" refers to coxsackievirus A) but it can also be caused by coxsackievirus B or echoviruses. Most cases of herpangina occur in the summer, affecting mostly children. However, it occasionally occurs in adolescents and adults. It was first characterized in 1920.

There is low or very-low quality evidence that probiotics may be better than placebo in preventing acute URTIs. Vaccination against influenza viruses, adenoviruses, measles, rubella, "Streptococcus pneumoniae", "Haemophilus influenzae", diphtheria, "Bacillus anthracis", and "Bordetella pertussis" may prevent them from infecting the URT or reduce the severity of the infection.

Inflammation can spread to other parts of the gut in patients with typhlitis. The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.

Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation. More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death

In terms of pathophysiology, rhino virus infection resembles the immune response. The viruses do not cause damage to the cells of the upper respiratory tract but rather cause changes in the tight junctions of epithelial cells. This allows the virus to gain access to tissues under the epithelial cells and initiate the innate and adaptive immune responses.

Up to 15% of acute pharyngitis cases may be caused by bacteria, most commonly "Streptococcus pyogenes", a group A streptococcus in streptococcal pharyngitis ("strep throat"). Other bacterial causes are "Streptococcus pneumoniae", "Haemophilus influenzae", "Corynebacterium diphtheriae", "Bordetella pertussis", and "Bacillus anthracis".

Sexually transmitted infections have emerged as causes of oral and pharyngeal infections.

Smoking, especially heavy smoking, is an important predisposing factor but the reasons for this relationship are unknown. One hypothesis is that cigarette smoke contains nutritional factors for "C. albicans", or that local epithelial alterations occur that facilitate colonization of candida species.

Malnutrition, whether by malabsorption, or poor diet, especially hematinic deficiencies (iron, vitamin B12, folic acid) can predispose to oral candidiasis, by causing diminished host defense and epithelial integrity. For example, iron deficiency anemia is thought to cause depressed cell-mediated immunity. Some sources state that deficiencies of vitamin A or pyridoxine are also linked.

There is limited evidence that a diet high in carbohydrates predisposes to oral candidiasis. "In vitro" and studies show that Candidal growth, adhesion and biofilm formation is enhanced by the presence of carbohydrates such as glucose, galactose and sucrose.

Untreated, the infection may lead to rapid destruction of the periodontium and can spread, as necrotizing stomatitis or noma, into neighbouring tissues in the cheeks, lips or the bones of the jaw. As stated, the condition can occur and be especially dangerous in people with weakened immune systems. This progression to noma is possible in malnourished susceptible individuals, with severe disfigurement possible.

A minority of cases of infectious mononucleosis is caused by human cytomegalovirus (CMV), another type of herpes virus. This virus is found in body fluids including saliva, urine, blood, and tears. A person becomes infected with this virus by direct contact with infected body fluids. Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child. This virus is often "silent" because the signs and symptoms cannot be felt by the person infected. However, it can cause life-threatening illness in infants, HIV patients, transplant recipients, and those with weak immune systems. For those with weak immune systems, cytomegalovirus can cause more serious illnesses such as pneumonia and inflammations of the retina, esophagus, liver, large intestine, and brain. Approximately 90% of the human population has been infected with cytomegalovirus by the time they reach adulthood, but most are unaware of the infection. Once a person becomes infected with cytomegalovirus, the virus stays in his/her body fluids throughout his or her lifetime.

About 90% of cases of infectious mononucleosis are caused by the Epstein–Barr virus, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected person’s saliva, such as through kissing or sharing toothbrushes, cups, etc. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually become infected.

In developed countries, this disease occurs mostly in young adults. In developing countries, NUG may occur in children of low socioeconomic status, usually occurring with malnutrition (especially inadequate protein intake) and shortly after the onset of viral infections (e.g. measles).

Predisposing factors include smoking, viral respiratory infections and immune defects, such as in HIV/AIDS. Uncommon, except in lower socioeconomic classes, this typically affects adolescents and young adults, especially in institutions, armed forces, etc., or people with HIV/AIDS. The disease has occurred in epidemic-like patterns, but it is not contagious.

Among individuals being treated in intensive care units, the mortality rate is about 30-50% when systemic candidiasis develops.

Oral candidiasis is the most common fungal infection of the mouth, and it also represents the most common opportunistic oral infection in humans. In the Western Hemisphere, about 75% of females are affected at some time in their lives with a vaginal yeast infection.

Esophageal candidiasis is the most common esophageal infection in persons with AIDS and accounts for about 50% of all esophageal infections, often coexisting with other esophageal diseases. About two-thirds of people with AIDS and esophageal candidiasis also have oral candidiasis.

Candidal sepsis is rare. Candida is the fourth most common cause of bloodstream infections among hospital patients in the United States.

Enterocolitis or coloenteritis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manifestations of enterocolitis are frequent diarrheal defecations, with or without nausea, vomiting, abdominal pain, fever, chills, alteration of general condition. General manifestations are given by the dissemination of the infectious agent or its toxins throughout the body, or – most frequently – by significant losses of water and minerals, the consequence of diarrhea and vomiting.

Among the causal agents of acute enterocolitis are:

- bacteria: "Salmonella", "Shigella", "Escherichia coli", "Campylobacter" etc.;

- viruses: enteroviruses, rotaviruses, Norwalk virus, adenoviruses;

- fungi: candidiasis, especially in immunosuppressed patients or who have previously received prolonged antibiotic treatment;

- parasites: "Giardia lamblia" (with high frequency of infestation in the population, but not always with clinical manifestations), "Balantidium coli", "Blastocystis homnis", "Cryptosporidium" (diarrhea in people with immunosuppression), "Entamoeba histolytica" (produces the amebian dysentery, common in tropical areas).

Specific types of enterocolitis include:

- necrotizing enterocolitis (most common in premature infants)

- pseudomembranous enterocolitis (also called "Pseudomembranous colitis")

Tonsilloliths or tonsillar concretions occur in up to 10% of the population, frequently due to episodes of tonsillitis. While small concretions in the tonsils are common, true tonsilloliths or stones are rare. They commonly occur in young adults and are rare in children.

Rotavirus, norovirus, adenovirus, and astrovirus are known to cause viral gastroenteritis. Rotavirus is the most common cause of gastroenteritis in children, and produces similar rates in both the developed and developing world. Viruses cause about 70% of episodes of infectious diarrhea in the pediatric age group. Rotavirus is a less common cause in adults due to acquired immunity. Norovirus is the cause in about 18% of all cases.

Norovirus is the leading cause of gastroenteritis among adults in America, causing greater than 90% of outbreaks. These localized epidemics typically occur when groups of people spend time in close physical proximity to each other, such as on cruise ships, in hospitals, or in restaurants. People may remain infectious even after their diarrhea has ended. Norovirus is the cause of about 10% of cases in children.