This study used a cross-sectional design to examine the role of religious involvement within a stress-process framework. Participants were 252 urban, low-income HIV-seropositive African American mothers. The relationships among religious involvement, stress, coping responses, social support, and psychological distress were examined using structural equation modeling. The number of stressors reported by the mother was related to greater religious involvement, which in turn was negatively related to psychological distress. Furthermore, the results suggest that social support, active coping, and avoidant coping responses mediated the relationship between religious involvement and psychological distress. According to the present results, interventions to attenuate psychological distress in HIV-seropositive African American mothers might focus on increasing social support, promoting active coping, and decreasing avoidant coping. The present findings suggest that this may be accomplished, in part, by promoting involvement in religious institutions and practices. However, in light of the cross-sectional design used in the present study, and given that religion may have both positive and negative consequences, further research is needed to determine the extent to which promoting religiosity may increase or alleviate distress.