BackgroundMusculoskeletal pain (MSP) is the largest contributor to chronic pain and frequently occurs alongside other medical comorbidities. ObjectiveExplore the relationships between the presence of pain-related comorbidities, pain intensity, and pain-related psychological distress in patients with MSP. MethodsA longitudinal assessment of individuals 18–90 years old in the Midwestern United States beginning a new episode of physical therapy for MSP. Electronic medical records were assessed the full year prior for care-seeking of diagnoses for pain-related comorbidities (anxiety, metabolic disorder, chronic pain, depression, nicotine dependence, post-traumatic stress disorder, sleep apnea, and sleep insomnia). Pain intensity and pain-related psychological distress (Optimal Screening for Prediction of Referral and Outcome - Yellow Flags tool) were captured during the physical therapy evaluation. Generalized linear models were used to assess the association between pain intensity, psychological distress, and pain-related co-morbidities. Models were adjusted for variables shown in the literature to influence pain. Results532 participants were included in the cohort (56.4% female; median age of 59 years, Interquartile Range [IQR]:47, 69). Comorbid depression (beta coefficient (β) = 0.7; 95%CI: 0.2, 1.2), spine versus lower extremity pain ((β = 0.6; 95%CI: 0.1, 1.1), and prior surgery (β = 0.8, 95%CI: 0.3, 1.4) were associated with higher pain intensity scores. No pain-related comorbidities were associated with pain-related psychological distress (yellow flag count or number of domains). Female sex was associated with less pain-related psychological distress (β = −0.2, 95%CI: −0.3, −0.02). ConclusionsDepression was associated with greater pain intensity. No comorbidities were able to account for the extent of pain-related psychological distress.