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Encephalitis is most often caused by a viral infection. The specific viruses involved may vary. Exposure to viruses can occur through insect bites, food or drink, or skin contact. In rural areas, arboviruses that are carried by mosquitoes or ticks, or that are accidentally ingested, are the most common cause.

In urban areas, enteroviruses are most common, including Coxsackie virus, poliovirus, and echovirus. Other causes include herpes simplex infection, varicella (chickenpox or shingles), measles, mumps, rubella, adenovirus, rabies, West Nile virus, and only rarely, vaccinations.

Once the virus has entered the blood stream, it can localize in the brain causing inflammation of the brain cells and surrounding membranes. White blood cells invade the brain tissue as they try to fight off the infection. The brain tissue swells (cerebral edema) and can cause destruction of nerve cells, bleeding within the brain (intracerebral hemorrhage), and brain damage.

Encephalitis is uncommon. It affects approximately 1,500 people per year in the U.S. However, elderly people and infants are more vulnerable to a more severe course of the disease.