Knowledge regarding mortality as a potential consequence of being sickness absent because of musculoskeletal diagnoses is almost nonexistent. The association between sickness absence because of musculoskeletal diagnoses and risk of premature death was examined in a prospective, nationwide, population-based cohort study based on Swedish registers. Included were all 4,760,987 individuals who were living in Sweden December 31, 2005, aged 20 to 64 years, and not on disability or old-age pension. Those sickness absent in 2005 because of musculoskeletal diagnoses were compared to those sickness absent because of non-musculoskeletal diagnoses and to those with no sickness absence. Musculoskeletal diagnoses were categorized as follows: 1) artropathies/systemic connective tissue disorders; 2) dorsopathies; and 3) soft tissue disorders/osteopathies/chondropathies/other musculoskeletal disorders. All-cause mortality was followed from 2006 to 2009 and cause-specific mortality was followed from 2006 to 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. In models adjusted for socio-demographic factors, and morbidity, sickness absence because of all 3 categories of musculoskeletal diagnoses was associated with 1.3- to 1.5-fold increased risks of all-cause mortality (adjusted model, category 1 diagnoses, HR=1.50, 95% CI=1.38-1.63). Similar associations were observed among both women and men. Moreover, increased mortality risks due to tumors (HR=1.6-1.7), circulatory diseases (HR=1.2-1.5), mental disorders (HR=1.2-3.2), and suicide (HR=1.5-1.9) were observed among persons sickness absent because of musculoskeletal diagnoses. This nationwide cohort study reveals, for the first time, an increased risk of premature death among both women and men sickness absent because of musculoskeletal diagnoses after adjustment for several potential confounders.