Hypothesis : Cartilage Oligomeric Matrix Protein (COMP) is a non-collage nous glycoprotein, which occurs mainly in an articular cartilage. This protein increases under the influence of cytokines and growth factors as a result of various diseases that cause damage to cartilage, fragments of it are released into synovial fluid and then into blood (serum COMP). Objectives : To assess the value of serum COMP (sCOMP) as an inflammatory marker in Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Osteoarthritis (OA) patients, and to find its correlation with disease activity & bone mineral density changes (BMD). Methodology : This study was conducted on 100 subjects including ten healthy volunteers as group I, 30 RA patients (group II), 25 SLE patients (group III), and 35 patients with knee OA (group IV). In addition to the physical examinations, activity was assessed in RA and SLE patients. WOMAC index was also performed for OA patients. Assessment of sCOMP level was determined, in addition to assessment of bone mineral density changes by DEXA. Results : The mean values of sCOMP in RA, SLE and OA patients were 10.6 ± 3.8 U / l, 11.9 ± 3.1 U / l, and 10.9 ± 2.9 U / l respectively. In the control group it was 5.9 ± 1.1 U / l. Serum COMP level in RA patients was significantly higher in patients with DAS >3.7 (p<0.05) , and in patients with (ESR) value ≥ 40 mm / h compared with patients with ESR value < 40 mm / h (p < 0.05). A high significant elevation of sCOMP level was obtained in SLE patients with hemoglobin (Hb) < 11.0 g /l, as well as those with ESR ≥ 40 mm / h (p < 0.01). In addition, SLE patients with SLEDAI > 6 showed high significantly elevated sCOMP level than those with SLEDAI > 6 (p < 0.01). In OA patients, the level of sCOMP was significantly elevated in those with BMD < -2.5 than those with BMD ≥-2.5. High significant elevation was detected on comparing sCOMP level in either of group II, group III or group IV with group I (p < 0.01 for all). In RA patients a significant positive correlation was detected between the sCOMP level and disease activity score (DAS), Hb, ESR (r = 0.42, 0.39, 0.37 respectively) (p < 0.05 for all). In SLE patients a high significant negative correlation was found between the sCOMP level and Hb (r = -0.50, p < 0.01), and significant positive correlation was found between the sCOMP level and ESR (r = 0.40, p < 0.05). In OA patients a significant positive correlation was found between the sCOMP level and WOMAC index (r = 0.39), and high significant negative correlation between the sCOMP level and T-score (r = -0.60, p>0.01). Conclusions: Measurement of sCOMP is valuable for monitoring inflammation in both inflammatory e.g. (SLE, RA) and degenerative joint diseases e.g. (OA) we observed its correlations with activity parameters in RA and SLE. More over OA patients had significant and high significant positive correlation of sCOMP with WOMAC index and the changes of bone mineral density (T-score) values respectively.