Musculoskeletal changes are the most common clinical manifestation of brucellosis. The main objective of this study was to provide a better understanding of this disease, while also attempting to identify potential markers that can identify the early stage musculoskeletal changes associated with human brucellosis. In this case-control study, 41 male early-stage brucellosis patients (within 6 months of diagnosis) who had not received drug therapy and 44 matched controls were examined. Venous blood samples were collected and serum pyridinoline (PYD), type II collagen cleavage neoepitope (C2C) and osteocalcin (OC) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). In the brucellosis group, the median serum levels of PYD (278.53 µg/L), C2C (82.23 µg/L) and OC (8.41 µg/L) were significantly elevated relative to the control group (Z = 5.686, 3.997, 3.579; P = 0.000). Serum PYD, C2C, and OC levels were increased in early-stage male brucellosis patients, and these factors appear to have promise as potential indicator biomarkers that can reflect the osteoarticular changes that occur in the early stage of human brucellosis.