Background: Osteoarthritis (OA) is the highest prevalent degenerative joint condition, leading to joint discomfort and impaired function. Objective: This study aimed to  examin the relationship among serum interleukin-6 (IL-6) and knee osteoarthritis (KOA) signs as well as the relationship among serum IL-6 and radiographic severity in cases with primary KOA. Methods: This case-control research involved 50 primary KOA cases and 50 controls. Signs were measured through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: Serum IL-6 was significantly elevated in OA cases than controls. WOMAC in OA cases ranged from 0 to 95 and Kellegren-Lawrence (KL) score mean was 2.7 ± 0.76.Serum IL-6 was significantly correlated with pain, physical function score, and radiographic score.Regression analysis revealed that IL-6 had a higher influence on WOMAC and KL score. Conclusion: Serum IL-6 is elevated in KOA cases. In addition, serum IL-6 is associated with OA signs and radiographic severity.