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Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18,1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socio-economic status. The numbers of excess deaths associated with high stress were 69 among persons without multi-morbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity. [ABSTRACT FROM AUTHOR]