In most people (80%), infection causes no symptoms. In others, the virus causes mild flu-like symptoms known as West Nile fever. The virus is able to pass the blood-brain barrier, and the most serious effects (in 0.7% of the infected) are encephalitis (inflammation of the brain) and meningitis (inflammation of the lining of the brain and spinal cord), both of which can be fatal. Persons over 50 years of age are at higher risk of developing severe disease, the symptoms of which include fever, nausea, and changes in mental status. In rare cases (first reported October 2002), patients may develop temporary blindness which can last from one to four weeks. This will begin as partial blindness but the person's vision will rapidly deteriorate to total blindness. Very rarely meningismus (stiff neck) is reported.

Symptoms develop 3–15 days after infection. No effective treatment is known. The disease can be diagnosed by employing an ELISA test detecting IgM antibodies against the virus. Several related viruses also cause encephalitis and result in similar antibodies, but a final diagnosis can be made with a further test.