Chondrocytes and synovial cells synthesize Cartilage Oligomeric Matrix Protein (COMP) when activated by proinflammatory cytokines. The aim of this study was to analyze and compare ultrasound parameters of joint inflammation, effusion and synovitis with the levels of COMP in the serum of patients with primary osteoarthritis. Ultrasound was done and the concentration of COMP (ng/mL was examined in 88 patients. 75% of patients had effusion (size 10.13±4.35 mm), 62.5% had effusion in lateral recessus (LR), 28.4% (size 8.53±2.27 mm) in suprapatelar (SR), and 27.3% (size 11.38±4.44 mm) in medial (MR). 67% of patients had synovitis size 4.84±3.57 mm in SR, 3.15±1.86 mm in MR; and 6.09±2.80 mm in LR. 17.0% of patients had nodular type of synovitis, 30.7% had diffusive, and 19.3% nodular - diffusive. There was a significant link between the size of synovitis and effusion in SR (r = 0.966, p = 0.000), MR (r = 0.812, p = 0.009) and LR (r = 0.886, p = 0.003). The median of COMP concentration was 54 (44.5-58) ng/mL in patients without effusion. In those with effusion it was 57 (48.75-64.25) ng/mL (p = 0.030). Without synovitis it was 52 (45.5-58) ng/mL, with synovitis 58 (50-66) ng/mL, (p = 0.006), diffusion type synovitis 60 (50-67) ng/mL, nodular 57 (50-62) ng/mL, nodular-diffusion 54 (44.5-66.5) ng/mL (p = 0.014). With longer osteophytes the median of COMP was 56 (48-64) ng/mL, with shorter osteophytes 55 (46.5-59) ng/mL (p = 0.000). Cartilage oligomeric matrix protein has a moderate significance in the assessment of disturbance of the metabolism of synovial and cartilage tissue in patients with knee osteoarthritis (sensitivity = 59%; specificity = 50%; cut off = 53.5 ng/mL).