This study examined the predictor and moderator effects of ego resilience and mindfulness on the relationship between academic stress and psychological well-being in a sample of Ghanaian college students (N = 431). The results indicated that academic stress was positively associated with both anxiety and depression and that mindfulness and ego resilience were both negatively associated with anxiety and depression. Mindfulness buffered the positive relationship between academic stress and depression but not anxiety. In contrast, ego resilience buffered the positive relationship between academic stress and anxiety but not depression. Implications for the study’s findings are discussed and recommendations for future research are presented.