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Abstract Background: Hepatitis C virus (HCV) is a global pathogen and a leading cause of morbidity and death. Epidemiological evidence highlights chronic HCV infection as the main cause of cirrhosis, hepatocellular carcinoma as well as other extrahepatic diseases. Meanwhile, histological evaluation of liver biopsy is the principal method used for assessing the severity of liver disease. Efforts are being exerted to replace liver biopsy with alternative non-invasive methods. HCV is known to target mitochondria, therefore mitochondrial dysfunction is anticipated to be a cornerstone in hepatic disease progression. In this light, a unique, liver-specific intramitochondrial enzyme, carbamoyl phosphate synthetase 1 (CPS1), could be useful in the prognosis of hepatic disease. Aim of the work: This study aimed at quantifying CPS1 in the serum of patients at different stages of chronic hepatitis C in relation to liver tissue CPS1 and mitochondrial counts, using light (LM) and electron microscopy (EM) respectively. This would assess its value as a marker of mitochondrial dysfunction and liver disease progression in chronic hepatitis C patients. Materials and methods: This research included 72 different HCV chronically infected patients and 15 healthy controls. Percutaneous liver biopsies were collected and processed for LM and EM examination. group (F1+F2) represented moderate fibrosis and group (F3+F4) represented severe fibrosis. Blood samples were collected for tests including CBC, platelet count, PT, ALT, AST, total bilirubin, albumin and urea using the standard kits. In addition, serum CPS1 was evaluated using ELISA |