Maternal perinatal depression (PND) may interfere with effective perinatal HIV care. In order to begin examining the prevalence and characteristics of PND in HIV-infected women, we analyzed data from the medical records of all HIV-infected women who had received perinatal care in the Maternal-Child and Adolescent Center for Infectious Diseases and Virology at LAC/USC Medical Center from 1997 through 2006. Data from 273 individual women (328 live births) were analyzed. Demographic, medical history, psychosocial, pregnancy related, and HIV-related factors measured during the perinatal period were examined for an association with PND using multivariate logistic regression with generalized estimating equations to account for the within subject correlation due to multiple births per mother. The overall prevalence of PND was 30.8%. Multivariate analysis showed that PND was significantly associated with substance abuse during pregnancy (odds ratio [OR] = 2.81, 95% confidence interval [CI]: 1.35-5.82) and past history of psychiatric illness (OR = 3.72, 95% CI: 2.06-6.71). Compared to mothers with CD4 nadir greater than 500 cells/mm3, mothers with a CD4 nadir during pregnancy #200 cells=mm3 were 3.1 times more likely to experience PND (OR = 3.01, 95% CI: 1.32-6.88). Women who had antiretroviral (ARV) medications adherence problems during pregnancy were more likely to experience PND than women who were adherent (OR = 2.14, 95% CI: 1.08-4.23). These preliminary results suggest that rates of PND among HIV-infected women are substantial. We conclude that pregnant HIV-infected women should be routinely screened for PND. Prospective studies examining the bio-psycho-social markers of PND in HIV-infected women are indicated.