West Nile virus infection can result in prolonged subjective complaints of cognitive and functional decline even in the absence of a neuroinvasive form of infection. Persistent cognitive and functional complaints could be a result of general somatic symptoms, emotional distress, or residual central nervous system damage or dysfunction. Most studies of cognition in postacute West Nile virus infection rely on self-report. This descriptive study aimed to document cognitive deficits in a sample of the 2003 infected population reported in New Mexico. Patients with clinically defined neuroinvasive disease or who were impaired on brief mental status screening were seen for comprehensive neuropsychological assessment. We found that one year after symptom onset, more than half of the sample had objectively measurable neuropsychological impairment in at least two cognitive domains. Impairment was not related to subjective complaints of physical or emotional distress, or premorbid intellectual abilities. Persistent cognitive impairment in West Nile virus infection may be due to prolonged or permanent damage to the central nervous system.