This study investigated the influence of coping strategies on quality of life of mothers living with HIV over 24 months postpartum. Fifty-six Brazilian mothers living with HIV answered quality of life and coping scales at pregnancy, 3rd, 12th, and 24th month postpartum. Mixed model longitudinal regressions were conducted. Quality of life improved in physical, level of independence, and environmental domains over time. While problem-focused coping was positively associated with all changes in quality of life, emotionally focused strategies showed inverse association with physical and environmental quality of life. Health care should help mothers living with HIV to actively cope with HIV together with political and community efforts to address their social vulnerability.