Objectives: To evaluate the prevalence of and factors associated with depression among HIV-infected homeless and marginally housed men. Design: Cross-sectional study. Participants and Setting: Homeless and marginally housed men living with HIV in San Francisco identified from the Research on Access to Care in the Homeless (REACH) Cohort. Measurements: The primary outcome was symptoms of depression, as measured by the Beck Depression Inventory (BDI). Multivariate logistic regression was used to identify associations of sociodemographic characteristics, drug and alcohol use, housing status, jail status, having a representative payee, health care utilization, and CD4 T lymphocyte counts. Results: Among 239 men, 134 (56%) respondents screened positive for depression. Variables associated with depression in multivariate analysis included white race (adjusted odds ratio [AOR]=2.2, confidence interval [CI]=1.3 to 3.9), having a representative payee (AOR=2.4, CI=1.3 to 4.2), heavy alcohol consumption (AOR=4.7, CI=1.3 to 17.1), and recently missed medical appointments (AOR=2.6, CI=1.4 to 4.8). Conclusions: Depression is a major comorbidity among the HIV-infected urban poor. Given that missed medical appointments and alcohol use are likely indicators of depression and contributors to continued depression, alternate points of contact are necessary with many homeless individuals. Providers may consider partnering with payees to improve follow-up with individuals who are HIV-positive, homeless, and depressed.