Most cases of West Nile encephalitis virus (WNV) infection are asymptomatic. In cases where WNV is symptomatic, patients usually experience high fever of sudden onset, myalgia, headache, and gastrointestinal symptoms, accompanied by a macular erythematous rash in a quarter to half of cases. More severe infections manifest as a poliomyelitis. Immunocompromise and immune senescence confer an increased risk of severe central nervous system (CNS) infection. Patients with human immunodeficiency virus (HIV) infection are therefore more susceptible, but, because the symptoms of WNV infection may be attributed to other CNS syndromes common in HIV patients, it is likely that the presence of WNV infection is underdiagnosed and underreported. We present a patient with severe WNV infection who was found to be HIV positive, who also suffered hearing loss. Several key differences in the presentation of WNV infection and Guillain-Barré syndrome that have treatment implications are discussed.