Background: rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. Cartilage oligomeric matrix protein (COMP) is one of markers used for early predicting joint destruction and disease activity in RA disease. Objective: in the present study we evaluated the role of COMP as diagnostic marker in RA patients in comparison with other traditional markers and its correlation with disease activity parameters. Patients and Methods: blood samples were collected from 50 patients newly diagnosed with rheumatoid arthritis (Group I) and also from 30 healthy subjectsas a control group (Group II).Serum level of COMP was measured by enzyme-linked immunosorbent assay (ELISA). Results: there was a high significant difference between the RA patients group and the control group regardingserum COMP level. Also, there was a significant correlation between serum COMP level with clinical and laboratory data of active RA patients. Conclusions: serum COMP could be useful for early diagnosis of rheumatoid arthritis and also could be used as a marker of disease activity and joint destruction.