Background: The present study investigated the prevalence of depression in HIV-positive individuals and its association with adherence to highly active antiretroviral therapy (HAART). Methods: HIV-positive (n = 80) and HIV-negative (n = 20) participants were assessed for depression and adherence via clinical interview and self-reporting. Results: Fourteen percent of the HIV-seropositive group met the criteria for current mood disorder compared with 5% of controls. Similarly, 39% of the HIV-seropositive participants met the criteria for a past major depressive episode compared with 15% of controls. Non-adherence to HAART was reported by 30.5% of those prescribed HAART and was significantly associated with living alone and relationship status. Conclusions: The present study found compromised psychological health in people living with HIV infection. It is recommended that health professionals continue to screen for depression, relationship status and living situation to ensure adherence to HAART.