Given that diet, physical activity, and social support are associated with depression, we examined whether a health promotion intervention designed to modify these factors in low-income, postpartum women would reduce depressive symptoms. This study used a randomized, controlled design to examine the effect of the Just for You (JFY) Program, an educational intervention promoting healthy lifestyles through home visits by nutrition paraprofessionals and motivational telephone counseling, on postpartum depressive symptoms. A total of 679 women income-eligible for the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) were recruited at 6-20 weeks post delivery and randomized to Usual WIC Care or JFY. Using an intention-to-treat analysis, the authors modeled depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) among 403 women (59%) completing follow-up at a mean of 15 months infant age, adjusting for baseline CES-D, age, household income and randomization strata (body mass index (BMI), race/region). As a secondary analysis, the authors evaluated potential mediators related to social support and self-efficacy to change one or more health behaviors targeted by the intervention. Women randomized to JFY reported 2.5 units lower CES-D score (P = 0.046) compared with those receiving Usual WIC Care alone. This relationship was attenuated by change in self-efficacy (β = -2.3; P = 0.065), suggesting this construct may partially have mediated the effect of JFY on maternal depressive symptoms. A health promotion intervention delivered through home visits and telephone calls can reduce depressive symptoms at 15 months postpartum among low-income, ethnically diverse women.