Background: Hepatitis C virus infection represents a serious epidemic problem in Egypt, it has the highest presence of the infection globally. Liver cirrhosis and hepatocellular carcinoma is mainly resultedfromchronic infection with Hepatitis C virus. Many direct antiviral agents have been utilized for treatment, but the hepatotoxicity of those drugs still rarely recorded. Objectives: We conducted this study to evaluate the drug-induced toxicity of sofosbuvir and ribavirin. Methods: Thirty two female albino rats were divided into four equal groups; Group one included rats which were administered orally with sofosbuvir (0.01 mg/kg body weight/day) suspended in distilled water. Group two included rats which were administered orally with ribavirin (0.0227 mg/kg body weight/day)suspended in distilled water. Group three included rats which were administered with a combination of sofosbuvir and ribavirin (0.01 and 0.023 mg/kg body weight/day, respectively)suspended in distilled water. Group 4 consisted of untreated animals and were served as control group. Results: The present study found a significant decrease in mean corpuscular volume and mean corpuscular haemoglobin values and a significant elevationofred blood corpuscles distribution width percentage in groups treated with ribavirin. Moreover, a significant elevation of aminotransferases, alkaline phosphatase, ammonia, total bilirubin and malondialdhyde were found in the treated groups as well. Conclusions: Sofosbuvir plus ribavirin can induce some hepatotoxicity in normal rats characterized by elevations in aminotransferases and microcytic hypochromic anaemia.