Apolipoprotein D (ApoD) is a 25-30 kDa glycoprotein, as a distinct component of the human plasma lipoprotein system. Its known biological functions are mainly related to lipid metabolism. The purpose of this study was to explore the potential role of ApoD concentration in knee osteoarthritis (KOA).This study was performed in a population of 113 KOA subjects and 97 healthy controls. Serum ApoD was detected using the commercial ELISA kit (Cusabio, Wu Han, China, Cat No. CSB-EL001935HU). Radiographic progression was evaluated using Kellgren-Lawrence (KL) classification. The clinical severity of KOA was assessed by visual analog score (VAS), Hospital for special surgery (HSS) knee score disease duration and TNF-α. Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of ApoD in radiographic progression.The serum ApoD level of patients with KOA was significantly lower than that of healthy controls. The serum ApoD level was negatively correlated with KL grades, VAS score, disease duration, TNF-α concentrations. On the contrary, it was positively correlated with HSS score. However, there was no correlation between this serological indicator and which side was affected. ROC curve analysis indicated that attenuated serum ApoD could serve as an appropriate biomarker concerning the diagnosis of KOA.Serum ApoD concentration was correlated with the presence and severity of KOA.© 2022. The Japanese Society Bone and Mineral Research.