Cartilage oligomeric matrix protein (COMP) is a biomarker of fibrosis in lung and skin. In this exploratory study we investigated the biomarker potential of COMP in chronic hepatitis C (CHC). We included consecutive patients with CHC admitted to the Department of Infectious Diseases, Lund University Hospital. COMP was analysed in serum using ELISA. The correlations between COMP and liver fibrosis, determined by transient elastography (TE) (n = 47) and liver biopsy (n = 28) were assessed. We also studied COMP prospectively in relation to antiviral treatment (n = 10). COMP correlated with the degree of liver fibrosis as assessed by TE (r = 0.71, p < 0.001) and liver biopsy (rs = 0.65, p < 0.001). After successful treatment of CHC, COMP decreased from 18 to 13 U/l (p = 0.011). We suggest that COMP is associated with the stage of liver fibrosis in CHC. The biomarker potential of COMP in CHC warrants further investigation.