Persons dually diagnosed with severe mental illness (SMI) and substance use disorder (SUD) have disproportionately high rates of HIV and other sexually transmitted infections (STIs). This study examined the relationship between multiple sexual risk behaviors among persons with active, remitted, and no SUD. Participants were 152 adults with SMI recruited from multiple treatment sites. A structured interview assessed the participants' psychiatric, psychosocial, and behavioral factors. Rates of sexual risk behavior in the past 3 months were high and differed across the SUD groups. Multivariate logistic regression models found that lifetime SUD predicted sexual activity and partner-related risk whereas active substance abuse predicted condom-related risk. The results also support indirect effects of interpersonal and psychiatric factors (e.g., romantic partnership and psychotic disorder). Findings underscore the need for integrated HIV/STI prevention interventions targeting dually diagnosed patients.