The aim is to study how serum concentration of Dickkopf-1 (DKK1) and Sclerostin (SOST) varies in patients before and after undergoing total joint arthroplasty (TJA). A total of 104 patients undergoing TJA were included in this study. Serum DKK1 and SOST were measured at 1 day before and 1, 3, and 5 days after surgery. DKK1 levels were highest at 5 days’ postoperation, increasing to 25.17% above preoperation levels (P < .01), while SOST levels were lowest at 3 days’ postoperation, falling to 18.71% below preoperation levels (P < .05). Serum levels of DKK1 and SOST showed opposite trends in the days following TJA. Our research describes for the first time the perioperative changes observed in serum DKK1 and SOST levels of osteoarthritis (OA) patients undergoing TJA. Increased DKK1 and decreased SOST levels may help maintain the equilibrium of the WNT pathway in OA patient's postsurgery.