Musculoskeletal conditions are a major cause of ill health and disability. Inadequate health literacy may partly explain why musculoskeletal self-management programs are not effective for some patients. This study prospectively evaluated the impact of patients' health literacy level on their musculoskeletal pain and physical function (PF) following usual primary care. Primary care patients (N = 4,720) who had consulted for musculoskeletal pain were mailed a baseline questionnaire; responders were sent a 6-month follow-up questionnaire. The measure of health literacy used was the single-item Literary Screener at baseline, and the outcomes were PF and pain intensity at the 6-months follow-up. Analysis was conducted by linear regression. The number of patients who responded was 1,890 (40%); 17.3% (95% CI [15.6%-19%]) of them had inadequate health literacy. Inadequate health literacy was associated with older age (p < .05), lower education, mental health, and comorbidities (all p < .001), but not by gender (p = .642). At the 6-month follow-up stage, patients with inadequate health literacy had lower PF (mean difference -12.2; 95% CI [-16.7, -7.6]) and higher pain intensity (mean difference 1; 95% CI [0.6, 1.4]), which was adjusted for age, gender, education, mental health, and comorbidities. Differences in PF and particularly pain scores between patients with inadequate and adequate health literacy increased over 6 months. Future studies should develop interventions that better support patients who have musculoskeletal pain with inadequate health literacy to successfully manage their pain. [HLRP: Health Literacy Research and Practice. 2018;2(4):e214-e220.].