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Self-rated health (SRH) is associated with morbidity and mortality in HIV-uninfected populations but is understudied in HIV. Substance use may affect SRH in addition to its deleterious effect on HIV disease. This analysis aimed to estimate SRH and substance use prevalence and evaluate factors associated with poor SRH among individuals in HIV care in Rio de Janeiro, Brazil. A convenience sample of HIV-infected adults completed one item of SRH, the Alcohol, Smoking and Substance Involvement Screening Test, and the Patient Health Questionnaire-2 (PHQ-2). Logistic regression models identified factors associated with poor SRH. Participants’ (n = 1029) median age was 42.9 years, 64.2% were male, and 54.5% were nonwhite. Poor SRH was reported by 19.5% and the use of alcohol, tobacco, marijuana, and crack/cocaine by 30.1, 19.5, 3.9, and 3.5%, respectively. Less than high school education (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI]: 1.08–2.20), lack of sexual activity in previous 12 months (aOR 1.53, 95% CI: 1.01–2.30), crack/cocaine use (aOR 3.82, 95% CI: 1.80–8.09), positive PHQ-2 screen (aOR 3.43, 95% CI: 2.09–5.62), and HIV-1 RNA ≥40 c/ml (aOR 2.51, 95% CI: 1.57–4.02) were significantly associated with poor SRH as identified by logistic regression analyses. Alcohol, marijuana, and sedative use were not significantly associated with poor SRH. These results emphasize the need for substance use and mental health screening and treatment in this population. Further research may elucidate the consequences of poor SRH on treatment adherence, morbidity, and mortality in HIV-infected individuals.