BACKGROUND:This study expands research on the substance abuse, intimate partner violence, human immunodeficiency virus (HIV), and depression syndemic theory for Hispanic women. We hypothesized relationship power and partner communication would be related to the syndemic. METHODS:Data were used from the baseline assessment of an effectiveness trial of SEPA (Salud/Health, Educación/Education, Prevención/Prevention, and Autocuidado/Self-care), an HIV/sexually transmitted infection risk reduction program for Hispanic women. Hispanic adult women (n = 320) completed measures (in Spanish or English) of relationship power, partner communication about HIV, and acculturation. The syndemic was defined with a factor model of substance abuse, intimate partner violence, risk for HIV/sexually transmitted infection, and depression using structural equation modeling. RESULTS:Controlling for acculturation and education, relationship power was inversely related to the syndemic factor (β = -0.49, p < .001), but partner communication was not (β = 0.14, p = .054). Acculturation and education were also related to the syndemic factor. These variables combined accounted for more than one-half (53%) of the variance in the syndemic factor. CONCLUSIONS:Findings suggest the need to develop and test interventions that address the power dynamics of intimate relationships as a means of reducing health disparities among Hispanic women.