Background: Osteoarthritis (OA) is a common joint disease. The Kellgren-Lawrence (KL) classification is used to assess knee OA severity through radiographic images. Monitoring OA can also be done by measuring biological markers of cartilage degradation. Studies suggest that cartilage oligomeric matrix protein (COMP) levels increase with the severity of cartilage damage.This study is plan to examine the level of serum cartilage oligomeric matrix protein and compare it with the severity of kneeosteoarthritisbased onthe KL grading scale. Methodology:50 primary knee osteoarthritis patients and 50 controls aged 40 and above underwent radiographic assessment (K-L grading) based on the American classification of rheumatology. The serum COMP level is estimated for all subjects by Enzyme-linked immunosorbent assay. Results:The mean of serum COMP (ng/ml) is 237.11 ±177.61 in the patient group, whichis significantly higher than the mean COMPof the control group, 149.78 ±108.01, with p= 0.004. The mean of Serum COMP levels (ng/ml) are measured between control and different grades shows statistically significant difference. Sub-group analysis showed a significant difference in mean COMP levels between the control group and Grades 3 and 4. Conclusion: In the present study,we found that serum COMP levels can effectively distinguish individuals with knee osteoarthritis (OA) from those without OA. Additionally, COMP levels are significantly higher in advanced OA stages compared to normal and early-stage OA, indicating the serum level of COMP can be used todiagnose normal and diseased individuals andto assess different grades of severity of disease.