OBJECTIVES: The primary objective was to compare sensory processing measures in people attending specialist orthopaedic consultation for management of persistent shoulder pain with control participants. The secondary objective was to compare the groups' sociodemographic, clinical, general health and lifestyle, and psychological characteristics. DESIGN: Observational cross-sectional. METHODS: Participants with shoulder pain for ≥3 months, who attended a public hospital orthopaedic department (n = 119), and community participants without shoulder pain (n = 44) underwent a standardized quantitative sensory testing protocol, measuring pressure pain threshold, temporal summation, and conditioned pain modulation. Sociodemographic, clinical, general health and lifestyle, and psychological characteristics were also collected. RESULTS: Participants with shoulder pain had significantly lower pressure pain thresholds at all sites (ie, local and widespread mechanical hyperalgesia) and significantly decreased conditioned pain modulation effect (ie, descending inhibition of nociception) than control participants. There was no significant difference between groups for temporal summation. Participants with shoulder pain had decreased general health and function, less healthy lifestyles, and poorer psychological health compared with controls. CONCLUSION: People referred to specialist orthopaedic care for management of persistent shoulder pain had clinical signs of altered sensory processing and poor health outcomes. J Orthop Sports Phys Ther 2024;54(10):1-10. Epub 25 July 2024. doi:10.2519/jospt.2024.12512.