Objectives: To clarify the effectiveness of perinatal social support interventions in reducing postpartum depression among minority, low-income women. Methods The Transdisciplinary Research Consortium for Gulf Resilience on Women’s Health supported a community-based participatory research project to improve perinatal health among low-income, first-time pregnant women living in a vulnerable Gulf Coast region. Community health workers (CHWs) were partnered with recruited women, and used a mix of mobile technology and home visits to develop a supportive relationship during the perinatal period. Results Women enrolled in the CHW-led intervention had lower (F: 2.38, p = 0.04) average postpartum depression scores (EPDS) 6 months postpartum than a comparison population. The difference, however, was not seen among women in the intervention group who reported relatively poor relationships with their CHWs. Conclusions for Practice Results reinforce the evidence that perinatal social support can affect postpartum depression outcomes. CHWs are increasingly utilized by public programs to reach at-risk populations. We discuss the potential efficacy of CHW programs, but also, the need to pair outreach with effective monitoring and evaluation of the relationship development between CHW and clients.