The present study aimed to detect serum fetuin-A levels in knee osteoarthritis (OA) patients and to investigate their correlation with clinical severity. We enrolled 215 knee OA patients and 76 healthy controls. We measured serum fetuin-A levels by enzyme-linked immunosorbent assay and assessed the correlation between serum fetuin-A levels and Kellgren-Lawrence grades as well as Western Ontario and McMaster Universities Arthritis Index scores in OA patients. Our results demonstrated that serum fetuin-A levels were independently and negatively correlated with greater clinical severity in OA patients.