Previous studies have found that positive self-perceptions of aging (SPA) are associated with longer survival; however, a biological mechanism was unknown. We examined whether C-reactive protein (CRP), a marker of cumulative stress-related inflammation, mediates the relationship between SPA and survival. The SPA of participants aged 50 and older in the Health and Retirement Study (N = 4,149) were assessed at baseline. Inflammation was measured by the level of CRP 4 years later. Survival was followed for up to 6 years. As hypothesized, CRP mediated the impact of SPA on survival. Following the steps of a mediation analysis, positive SPA at baseline predicted lower CRP after 4 years (β = -.29, p = .03) and longer survival in the 2 years following the CRP measurement (β = .20, p =.003); additionally, lower CRP predicted longer survival, after adjusting for positive SPA (β = -.02, p = .0001). All models adjusted for baseline age, CRP, health, sex, race, and education. It was found that lower CRP partially mediates the relationship between positive SPA and longer survival. Hence, this study presents a novel pathway to explain the process by which positive SPA extend longevity.