Objective: Musculoskeletal pain and avoidant coping predicts sickness absence, but how these 2 predictors relate to each other is unknown. We examined the main and combined effects of musculoskeletal pain and avoidant, behavioural coping on incidence of sickness absence. Design and subjects: Prospective cohort study of a sample of middle-aged Danes, economically active in 2006, reporting functional limitations due to musculoskeletal pain, n = 3115. Methods: Data included surveys from 2000 and 2006 and register data from 2007. Outcome was sickness absence exceeding 2 consecutive weeks in 2007. The main effect of self-reported pain frequency and avoidant coping on sickness absence was analysed by multivariate logistic regression. The combined effect was calculated as departure from multiplicativity and by the inclusion of a product term. Results: Daily pain and use of avoidant coping were both associated with sickness absence in multiple adjusted analyses, odds ratio (OR)daily pain = 1.83 (95% confidence interval (CI) 1.51-2.21) and ORavoidant coping = 1.52 (95% CI 1.24-1.88) (main effects). A modest combined effect of musculoskeletal pain and avoidant coping on sickness absence was suggested (p = 0.286). Conclusion: Avoidant coping and daily pain are both associated with sickness absence, but showed no strong signs of interactive effects. Clinicians should be aware of both factors.