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Associations between the sense of humor and survival in relation to specific diseases has so far never been studied.We conducted a 15-year follow-up study of 53,556 participants in the population-based Nord-Trøndelag Health Study, Norway. Cognitive, social, and affective components of the sense of humor were obtained, and associations with all-cause mortality, mortality due to cardiovascular diseases (CVD), infections, cancer, and chronic obstructive pulmonary diseases were estimated by hazard ratios (HRs).After multivariate adjustments, high scores on the cognitive component of the sense of humor were significantly associated with lower all-cause mortality in women (HR = 0.52, 95% confidence interval [CI] = 0.33–0.81), but not in men (HR = 0.88, 95% CI = 0.59–1.32). Mortality due to CVD was significantly lower in women with high scores on the cognitive component (HR = 0.27, 95% CI = 0.15–0.47), and so was mortality due to infections both in men (HR = 0.26, 95% CI = 0.09–0.74) and women (HR = 0.17, 95% CI = 0.04–0.76). The social and affective components of the sense of humor were not associated with mortality. In the total population, the positive association between the cognitive component of sense of humor and survival was present until the age of 85 years.The cognitive component of the sense of humor is positively associated with survival from mortality related to CVD and infections in women and with infection-related mortality in men. The findings indicate that sense of humor is a health-protecting cognitive coping resource.