This study examined the mediating effects of affect on the relationship between core self-evaluations (CSE) and life satisfaction in people with intellectual disabilities. The participants comprised 134 people (79 men and 55 women from southern Spain) with intellectual disabilities. All participants completed the core self-evaluations scale (CSES), the positive and negative affect scale (PANAS), and the satisfaction with life scale (SWLS). The results showed that high scores on the CSE were associated with higher life satisfaction. Moreover, positive and negative affect partially mediated the relationship between CSE and life satisfaction. The final model also showed two significant paths from CSE through positive and negative affect to life satisfaction. We present the limitations of the study and discuss the implications of the results for enhancing life satisfaction in people with intellectual disabilities.