Understanding and intervening to address health disparities is part of the expanding role of psychologists (Johnson, 2013). We drew on Hatzenbuehler's (2009) psychological mediation framework and Lick, Durso, and Johnson's (2013) conceptual pathways to lesbian, gay, and bisexual (LGB) physical health disparities to test a serial mediation model in which 2 types of cognitive appraisals (proximal minority stressors and coping self-efficacy) partially account for the association between perceived discrimination and prejudice (distal minority stressor) and self-reported physical health symptoms in a nationally recruited sample of 564 LGB individuals (270 women, 294 men) who participated in a web-based survey. Results indicated that perceived experiences of discrimination and prejudice were associated with expectations of rejection and internalized homonegativity. These 2 proximal stressors were associated with lower coping self-efficacy, and the combined cognitive appraisal pathways were associated with higher levels of self-reported physical symptom severity. The pathway through emotion-focused coping self-efficacy was particularly salient in accounting for the overall mediation. Interventions to address distal and proximal minority stressors and improve emotion-focused coping self-efficacy may be particularly helpful in reducing the negative effects of stigma on physical health.