The purpose of the current study was to examine whether syndemic stress in partnered gay men might undermine communication processes essential to the utilization of negotiated safety and other harm reduction strategies that rely on partners’ HIV status disclosure. Participants included 100 gay male couples (N = 200 individuals) living in the U.S., who responded to an online survey. Participants completed measures of five syndemic factors (depression, poly-drug use, childhood sexual abuse, intimate partner violence, and sexual compulsivity). They also reported on whether condoms were used during first intercourse together and the timing of first condomless anal intercourse (CAI) relative to HIV disclosure in their relationship. Results of binary logistic regression analyses supported the hypothesis that the sum of partners’ syndemic stress was negatively associated with condom use at first intercourse and with HIV disclosure prior to first CAI. Syndemic stress may contribute to HIV transmission risk between main partners in part because it accelerates the progression to CAI and interferes with communication processes central to harm reduction strategies utilized by gay men in relationships. Implications for prevention strategies and couples interventions, such as couples HIV counseling and testing, that facilitate communication skill-building, are discussed.