Women infected with HIV are at an increased risk for infection of Human Papillomavirus (HPV), developing cervical lesions, and developing cervical cancer. Prior research has suggested disruptions in the immune system as well as circulating levels of stress and gonadal hormones as possible explanations for the increase of HPV infection in women with HIV. Additionally, psychosocial factors such as symptoms of depression and distress have also been associated with HPV infection, as well as disruptions in immune and endocrinologial systems, suggesting a psychoneuroimmunological pathway to disease progression. It was hypothesized that HIV+HPV+ women assigned to a Cognitive Behavioral Stress Management (CBSM) intervention will experience improvements in disease status, immune markers, circulating stress hormones, and reductions of depression and distress symptoms. An exploratory investigation of the effects of CBSM in levels circulating reproductive hormones was also tested. Follow-up hypotheses tested whether CBSM effects on immune variables were explained by reductions in symptoms of depression, distress, NE, cortisol, and increases of DHEA-S. Additionally, it was hypothesized that CBSM effects on stress hormones would be mediated by reductions in distress and depression symptoms. Finally, it was hypothesized that improvements in immune parameters would be correlated with decreases in risk of cervical dysplasia at a 9 month follow-up. Participants were 71 women co-infected with HIV and HPV that were mostly of African American, Haitian, Latina, and Caribbean descent. Hierarchical regression analyses were performed and showed a significant CBSM effect in decreases on BDI somatic depression subscale scores and increases in NK cell counts. Additionally, there was a marginally significant effect of CBSM on increases in CD4+ T-cells and decreases in urinary NE output. The bootstrapping method evidenced a mediation model, where the relationship between group assignment and CD4+ cell counts was explained by lower BDI somatic scores. More research is necessary to fully elucidate the psychobiological trajectories of disease as immunological changes in our sample did not explain the reduced odds of dysplasia in the women assigned to the CBSM group.