Introduction <p>The COVID-19 pandemic intensified health, social, and economic inequities. This study examined its impact on the health and quality of life of U.S. LGBTQ+ midlife and older adults, focusing on how stigma and social resources moderated these effects.</p> Methods <p>A national cross-sectional survey of 685 LGBTQ+ adults aged 50 and older was conducted in 2022. Chi-square tests, Fisher’s exact tests, or ANOVA with Bonferroni correction were used to analyze differences in health risks, protective factors, and outcomes across sexual and gender identity subgroups. Hierarchical linear regression assessed associations between COVID-19 risks, stigma, and social resources with health and quality of life across two models: Model 1 included the main predictors, while Model 2 added sociodemographic data and interaction terms to test moderating effects.</p> Results <p>Sexually diverse participants reported higher COVID-19 risks, fewer social resources, greater stigma, and worse health and quality of life than their lesbian, gay, and bisexual peers. Housing instability and unmet basic needs were associated with greater depressive symptoms, poorer physical health, and lower quality of life. Social resources helped alleviate depressive symptoms, especially among those with unstable housing, while everyday discrimination reduced quality of life for those whose basic needs were met.</p> Conclusion <p>COVID-19 exacerbated health inequities among LGBTQ+ midlife and older adults, with significant differences across subgroups. These findings underscore the need for tailored interventions to promote health equity.</p> Policy Implications <p>To support LGBTQ+ midlife and older adults during public health crises, policy strategies should address housing stability, basic needs, anti-discrimination protections, and social support systems.</p>