Depression is one of the most prevalent psychiatric comorbidities of HIV and one of the greatest barriers to HIV self-care and adherence. Despite this, little consensus exists on how to best measure depression among people living with HIV/AIDS (PLWHA) in African settings. Measurement of depression among PLWHA may be confounded by somatic symptoms. Some research recommends excluding these items to enhance measurement validity; sensitivity may be lost with this approach. We sought to characterize depression among a cohort (N = 453) of PLWHA initiating antiretroviral therapy in Uganda via factor analysis of a widely used measure of depression, the Hopkins Symptom Checklist (HSCLD). Common factor analysis was performed, associations between HSCLD and the Mental Health subscale of the Medical Outcomes Study HIV (MOS-HIV) estimated, and a Cronbach's alpha calculated to examine validity. Factor analysis yielded two factors: (1) somatic-cognitive symptoms and (2) behavioral disengagement. Persons with more versus less advanced disease (CD4 cell count of ≤200 cells/mm(3)) showed no statistically significant differences in depression scores (1.7 vs. 1.7, P ≥ 0.5). Both factors were significantly associated with the MOS-HIV (P < .01). Factor one was highly reliable (α = .81); factor two had only modest reliability (α = .65). Somatic-cognitive symptoms of depression and disengagement from life's activities appear to be distinct components of depression in this sample. Consideration of somatic items may be valuable in identifying depression in this setting.