Objective: The aims of the current study were to investigate the associations between two aspects of well-being satisfaction with life and vitality - and all-cause mortality, and examine the impact of potential confounding factors on the associations. Methods: Baseline satisfaction with life was assessed using the Satisfaction With Life Scale (n = 7058) and vitality was assessed using the Short-Form 36 vitality subscale (n = 6987). The study sample consisted of midlife participants from the Copenhagen Aging and Midlife Biobank (CAMB) study conducted from 2009 to 2011. Deaths (n = 312) in the study sample in the follow-up period (mean of 8.6 years) were assessed using Danish register data. The hazard ratios of all-cause mortality according to satisfaction with life and vitality scores adjusted for potential covariates were examined with proportional hazard regression. Results: A one standard deviation increase on the SWLS and the SF-36 vitality scale was associated with a 39% (HR = 0.61, 95% CI = 0.55 & ndash;0.67) and 40% (HR = 0.60, 95% CI = 0.54 & ndash;0.66) decreased risk of mortality respectively, after adjustment for baseline sociodemographic factors. The associations remained significant after separate adjustment for lifestyle (SWLS: HR = 0.67, SF-36 vitality: HR = 0.67), health (SWLS: HR = 0.65, SF-36 vitality: HR = 0.64), depressive symptoms (SWLS: HR = 0.72, SF-36 vitality: HR = 0.71) and social factors (SWLS: HR = 0.76, SF-36 vitality: HR = 0.69). Conclusions: Satisfaction with life and vitality are of predictive value for mortality, independently of sociodemographics, lifestyle, health, depressive symptoms, and social factors.