Little is understood about why some youth from low-socioeconomic-status (SES) environments exhibit good health despite adversity. This study tested whether role models and “shift-and-persist” approaches (reframing stressors more benignly while persisting with future optimism) protect low-SES youth from cardiovascular risk. A total of 163 youth, ages 13–16, completed role model interviews and shift-and-persist measures while cholesterol and inflammatory markers, interleukin-6 (IL-6), and C-reactive protein were assessed. Low-SES youth with supportive role models had lower IL-6. Low-SES youth high in shift-and-persist also had lower IL-6. Shift-and-persist partially mediated the interaction of SES and role models on IL-6. Benefits were not found among high-SES youth. Identifying psychological buffers in low-SES youth has implications for health disparities.