Abstract The transition to college is a time of increased opportunity and stress spanning multiple domains. Adolescents who encounter significant stress during this transition may be vulnerable to adverse outcomes due to a “wear and tear” of the hypothalamic pituitary adrenal (HPA) axis. Latino/a students may be particularly at-risk for heightened stress exposure due to experiences of both minority-specific and general life stress. Despite this, little is known regarding the cumulative impact of multiple stressors on Latino/a students’ HPA axis functioning. The present study employed a “multi-risk model” approach to examine additive, common, and cumulative effects of multiple stress forms (general, academic, social, financial, bicultural, ethnic/racial discrimination) on diurnal cortisol in a sample of first-year Latino/a college students (N = 196; 64.4% female; M_age = 18.95). Results indicated that no stress forms were additively associated with the cortisol awakening response (CAR), but general stress was associated with a flatter diurnal cortisol slope (DCS) and bicultural stress was linked with a steeper DCS. A college stress latent factor was associated with a lower CAR, whereas a latent factor of discrimination was not associated with diurnal cortisol. Cumulative risk was linked with a lower CAR. Findings highlight the physiological correlates of various stressors experienced by Latino/a college students.