AbstractChronic musculoskeletal pain and sleep problems/disorders exhibit a recognized bidirectional relationship; yet, systematic investigations of this claim, particularly in a prospective context, are lacking. This systematic review with meta-analysis aimed to synthesize the literature on the prospective associations between sleep problems/disorders and chronic musculoskeletal pain. A comprehensive search across 6 databases identified prospective longitudinal cohort studies in adults examining the relationship between sleep problems/disorders and chronic musculoskeletal pain. Random-effects meta-analyses, using the Hartung–Knapp adjustment for 95% confidence intervals (CIs), were conducted, and all results were presented as odds ratios (ORs). Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Including 16 articles from 11 study populations (116,746 participants), meta-analyses indicated that sleep problems at baseline may heighten the risk of chronic musculoskeletal pain in both short term (OR 1.64, 95% CI 1.01-2.65) and long term (OR 1.39, 95% CI 1.21-1.59). The evidence for different sleep problem categories was very uncertain. Chronic musculoskeletal pain at baseline may increase the risk of short-term sleep problems (OR 1.56, 95% CI 1.02-2.38), but long-term evidence was very uncertain. The impact of only local or only widespread pain on short-term sleep problems was very uncertain, whereas widespread pain may elevate the risk of long-term sleep problems (OR 2.0, 95% CI 1.81-2.21). In conclusion, this systematic review with meta-analysis suggests that sleep problems are associated with an increased risk of chronic musculoskeletal pain, but the bidirectional nature of this relationship requires further investigation.