Depression has been shown to be a risk factor for serodiscordant unprotected anal intercourse (SDUAI) in some studies, but not others. Body mass index (BMI) has recently been associated with SDUAI; however, to date, no published study has investigated the interactive effect of depression and BMI on SDUAI. The current study assessed the association between depression, BMI, and SDUAI among HIV-positive MSM. Participants were 430 HIV-positive MSM recruited in a Boston community health center where they received primary care. Participants completed audio computer-assisted self interview (ACASI) measures. Objective height and weight and other clinical variables were accessed through participants' electronic medical records. Depression was positively associated with SDUAI. This association was significantly moderated by BMI. Elevated levels of depression were only associated with SDUAI for underweight participants. These findings suggest that underweight, depressed HIV-positive MSM may be particularly likely to engage in SDUAI.