The purpose of this article is to report the results of a study exploring the mediation effects of self-compassion and mindfulness on the relationship between mental distress and resilience among a national sample of college students (N = 260). The results of the structural equation modeling (SEM) serial mediation analysis revealed that mindfulness through self-compassion fully mediated the relationship between mental distress and resilience. Simple mediation demonstrated that self-compassion accounted for 79.3% of the total effect on resilience, while mindfulness accounted for 46.5%. After accounting for mental distress, follow-up regression analysis identified the mindfulness facet of non-reactive ([beta] = .19, p < . 01), and the self-compassion subscales of mindful awareness ([beta] = .32, p < . 01), common humanity ([beta] = .20, p < . 01), and reverse-scored isolation ([beta] = .17, p < . 05) to predict resilience. For students experiencing depression, anxiety, and loneliness, the dispositions of being present, non-judgmental, and accepting of life struggles may be particularly important for resilience and college persistence. Implications address how college counseling professionals can promote self-compassion and mindfulness on college campuses.