This study examined the relationship between three HIV-specific coping strategies (cognitive coping strategies, denial, and religious coping) and quality of life (QoL) in 90 HIV+, predominately minority women on highly active antiretroviral therapy. Religious coping was unrelated to QoL; however, use of cognitive coping strategies was related to greater QoL, and denial was related to poorer QoL. Baron and Kenny's model of mediation was then used to test perceived stress as a mediator of the relationships between denial and cognitive coping strategies and QoL. These relationships were both mediated by perceived stress. Results suggest that utilization of certain coping strategies may lessen or heighten perceptions of life stressfulness, thereby influencing QoL in this understudied population.