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To examine the relationship of musculoskeletal pain and depressive symptoms, occurring alone or both together, with self-rated current work ability and thoughts of early retirement.In a nationally representative sample drawn in 2000–2001, we studied actively working subjects aged 30 to 64 years (n = 4009).Musculoskeletal pain was associated with moderate/poor physical work ability (adjusted odds ratio [OR] = 2.9; 95% confidence interval [CI], 2.0 to 4.2) and mental work ability (OR = 1.6; 95% CI, 1.2 to 2.2). Depressive symptoms were associated with moderate/poor mental work ability only (adjusted OR = 4.2; 95% CI, 2.3 to 7.9). Moreover, only musculoskeletal pain was associated with thoughts of early retirement (OR = 1.4; 95% CI, 1.1 to 1.8). There was an interaction between musculoskeletal pain and depressive symptoms regarding physical work ability and thoughts of early retirement.Co-occurrence of musculoskeletal pain and depressive symptoms is strongly related to poor self-rated physical work ability.