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To investigate the impact of musculoskeletal pain on health-related quality of life and work productivity losses among US workers.Data from the 2008 US National Health and Wellness Survey were used. Among those currently employed aged 20 to 64 years (N = 30,868), workers with arthritis (n = 2,670), back (n = 4,920), and fibromyalgia (n = 439) pain were compared with workers without those respective musculoskeletal pain conditions.Arthritis, back, and fibromyalgia pain were all associated with significantly lower levels of health-related quality of life, often at clinically meaningful levels. All pain conditions were associated with higher levels of work productivity loss, even after adjusting for demographic and health characteristics.Musculoskeletal pain conditions were highly prevalent and associated with a significant burden. Improved management of these conditions may lead to improved productivity, benefiting both employers and workers alike.