Apathy is a prominent neuropsychiatric symptom associated with human immunodeficiency virus (HIV). The increased frequency of apathy in this population may reflect the direct involvement of the virus on the central nervous system (CNS), but the severity of apathy has not been shown to consistently relate to markers of disease activity or other neuropsychiatric complications of the virus. We examined the relationship between ratings of apathy and performance on measures of cognitive function and immune system status in a sample of HIV-infected patients. Apathy was significantly elevated among HIV-infected individuals compared to healthy comparison subjects. Apathy was significantly related to performance on measures of learning efficiency and a measure of cognitive flexibility. Ratings of apathy did not relate to CD4 cell count, but they were associated with disease duration. In addition, ratings of depression were independent of ratings of apathy. These findings suggest that apathy does not co-vary with a proxy measure of active disease status, but apathy does relate to several measures of cognitive dysfunction in patients with HIV. As such, the increased prevalence of apathy among HIV-infected adults may reflect HIV-associated neurologic dysfunction.