We aimed to apply syndemic theory to verify the association and reinforcing effects between psychosocial problems and multiple sexual partners (MSP) of men who have sex with men (MSM) in Shanghai, China. A cross-sectional study was conducted among 547 MSM in Shanghai, China using a face-to-face survey. Sociodemographic and psychosocial data were collected, as well as information on MSP and condomless anal sex. In the 6 months prior to the survey, 54.3% of the MSM sample had had MSP. Univariate analysis showed that self-esteem, depression, loneliness, sexual compulsivity, and involuntary subordination (IS) were associated with MSP. Sexual compulsivity (multivariate odds ratio [ORm] = 2.94, 95% CI = 1.76-4.91) and IS (ORm = 1.79, 95% CI = 1.14-2.81) remained significant in multivariate analysis. MSM with five or more psychosocial problems had greater odds of (adjusted odds ratios = 3.06, 95% CI = 1.49-6.25) having MSP in the previous 6 months than the non-syndemic group. Our findings provide preliminary confirmation of the additive relationship of syndemic psychosocial health conditions and MSP among MSM in Shanghai, China. An integrated intervention with special focus on sexual compulsivity and IS is needed.