BACKGROUND: Some studies have analyzed the relation between well-being and mortality but none of them have attempted to disentangle the differential influence that positive affect, negative affect, and evaluative well-being might have on mortality using a longitudinal design in the general population and measuring independently and accurately each component of well-being. The aim of the present study is to assess the association of these well-being components with mortality after adjusting for health and other lifestyle factors and to analyze whether this association is different in people with and without depression. METHODS: A nationally representative sample of 4753 people from Spain was followed up after 3 years. Analyses were performed with Cox regression models among the total sample and separately in people with and without depression. RESULTS: In the analyses adjusted for age, sex, and years of education, all three well-being variables showed separately a statistically significant association with mortality. However, after adjustment for health status and other confounders including the other well-being components, only positive affect remained as marginally associated with a decreased risk of mortality in the overall sample [HR = 0.87; 95% CI = 0.73-1.03], in particular among individuals without depression [HR = 0.82; 95% CI = 0.68-0.99]. CONCLUSION: Positive affect is inversely associated with mortality in individuals without depression. Future research should focus on assessing interventions associated with a higher level of positive affect.