The stress of co-infection with human immunodeficiency virus (HIV) and human papillomavirus (HPV), in race/ethnic minority women, may increase depression and immune decrements. Compromised immunity in HIV+ HPV+ women may increase the odds of cervical dysplasia. Thus, we tested the efficacy of a 10-week cognitive behavioral stress management (CBSM) group intervention and hypothesized that CBSM would decrease depression and improve immune status (CD4+ T-cells, natural killer [NK] cells). HIV+ HPV+ women (n = 71) completed the Beck Depression Inventory and provided blood samples, were randomized to CBSM or a control condition, and were re-assessed post-intervention. Women in CBSM revealed less depression, greater NK cells, and marginally greater CD4+ T-cells post-intervention vs. controls. Stress management may improve mood and immunity in HIV+ HPV+ lower-income minority women.