Osteochondrosis (OC) is a developmental disease in horses with a significant impact on the horse’s welfare and performance. The early disturbance of enchondral ossification progresses to inflammatory and healing process in older horses. Metabolic pathway analysis showed an obvious dysregulation of several signaling pathways related to cartilage formation and cartilage repair such as Wnt/β-catenin, Indian hedgehog and TGF-β signaling pathways. Other regulated genes appeared to be involved in high carbohydrate diet, abnormal insulin metabolism or inflammation. Sclerostin is an osteocyte-secreted soluble antagonist of the Wnt/β-catenin signaling pathway. It is crucial for osteoblast development and activity and is increased in naturally occurring lesions of equine osteochondrosis. The aim of this study is to compare the circulating sclerostin levels between OC-affected (n = 20) and healthy horses (n = 19). A significant linear regression between plasma sclerostin and age is observed especially in the healthy young horses. The mean plasma sclerostin concentration is significantly higher in young horses suffering from osteochondrosis compared to the control horses. These results reinforce the possible role of the Wnt/β-catenin signaling pathway in the OC pathogeny. The inhibition of this essential pathway could disturb the osteo-chondral differentiation. More studies are currently needed to define the eventual clinic interest of plasma sclerostin as future biomarker in bone and cartilage diseases.