SummaryA blind randomised study using two groups of age‐ and sex‐matched Quarter Horse foals was conducted by feeding a low copper diet containing 8 ppm of copper (Cu) and a control diet containing 25 ppm. Foals in the low‐Cu group had declining liver Cu values and developed osteochondritis (OCD), epiphysitis and limb deformities over a 6‐month period. Erosion and separation of cartilage from the subchondral bone in the dorsal facets of the cervical spine were the most consistent post‐mortem lesions. Foals fed the high‐Cu diet had no significant musculoskeletal lesions. Scoring of standing lateral cervical radiographs was a moderately sensitive (0.68) and specific (0.70) test and had moderate agreement with post‐mortem findings (κ = 0.35). Technetium scintigraphy of the limbs and cervical spine failed to detect occult or known lesions in the limbs and cervical spine. Microscopic examination of growth plates and metaphyseal bone from affected foals showed that fractures disrupted or displaced the normal growth plate architecture and interfered with orderly bone growth, similar to Cu deficiency in cattle. Bone morphometry indicated there was less subchondral bone volume in the distal cannon bone (P<0.005). Similarly, there were fewer newly formed trabeculae in the primary spongiosa (P<0.02) and metaphysis (P<0.07) of the distal tibia in the Cu‐deficient foals. Biochemical studies were limited to 4 control and 6 low‐Cu foals. Of the 6 low‐Cu foals, 4 were severely affected with multiple lesions. These assays showed significantly reduced collagen cross‐linking in the cartilage and bone articular cartilage of severely affected foals. The control group foals had articular and growth plate cartilage explants in tissue culture released increased amounts of gelatinase and proteoglycanase, reflecting increased matrix remodelling. Traditional concepts of osteochondritis have implicated a non‐specific defect in endochondral ossification. This study proposes a relationship between low copper intakes in fast‐growing horses, inferior collagen quality, biomechanically weak cartilage and OCD lesions. While all foals in the low‐Cu group were affected, only 5 of the 9 developed clinically significant lesions. This indicates that factors other than nutrition, such as individual variation in growth rate or genetic potential, still influence the expression of this syndrome.