Whereas a vast amount of research has demonstrated the association between core self-evaluations (CSE) and well-being indicators, few studies have specifically focused on the ways in which CSE might facilitate an increased well-being. This study assesses whether perceived stress might either be a potential mediator and/or moderator in the relationship between CSE and life satisfaction in two independent samples: middle-aged adults (N = 320) and young adults (N = 473). In both samples, participants completed a battery of questionnaires composed of a CSE scale, perceived stress scale and life satisfaction scale. Bootstrap analyses showed that perceived stress partially mediated the relationship between CSE and life satisfaction in both samples. However, moderation analyses failed to support that perceived stress moderated the influence of CSE on life satisfaction either in middle-aged adults or young adults samples. The implications of these findings for research and practice are discussed.