Hepatitis C virus (HCV) is a major public health problem. Soluble CD14 (sCD14) level was shown to be associated with HCV infection. In this study, we aimed to investigate the relationship between sCD14 concentration and disease progression, as well as the response to pegylated interferon/ribavirin (peg-IFN/RBV) therapy in Egyptian patients with chronic hepatitis C (CHC). The ELISA technique was used to test 80 patients with CHC and 20 healthy control persons for serum levels of sCD14 (pretreatment and after 12 weeks of treatment). CHC patients were 65 males and 15 females. Normal healthy controls included 20 age- and sex-matched volunteers. The mean age of the CHC patients was 39.94 years, while that of the controls was 39.2 years The serum sCD14 level was significantly higher in chronic HCV-infected patients (3.6±0.18 μg/mL) compared to healthy control subjects (3.1±0.18 μg/mL). The serum sCD14 level was significantly directly correlated with the hepatic fibrosis score (r=0.24, P=0.03), histological activity index (r=0.26, P=0.02), and serum aminotransferases [r=0.28, P=0.005 for alanine aminotransferase (ALT) and r=0.30, P=0.003 for aspartate aminotransferase (AST)]. The pretreatment sCD14 level was not significantly correlated to the treatment response, but it increased after 12 weeks of peg-IFN/RBV therapy and values were significantly higher in nonresponders (P=0.02). The pretreatment sCD14 level cannot predict the treatment response in chronic HCV patients receiving peg-IFN/RBV therapy. However, the serum sCD14 level after 12 weeks of treatment can serve as a negative predictor of treatment response.