Background: Hepatitis C virus (HCV) is a globally prevalent pathogen and a leading cause of death and morbidity. HCV drug therapy has depended on a combination of interferon and ribavirin that has been associated with severe side effects. However, sofosbuvir is an oral potent nucleotide inhibitor of HCV polymerase that has few drug interactions. Aim of the work: the present study was conducted to clarify the treatment efficacy and safety of the recent regimen, sofosbuvir and its direct physiological effect at HCV chronic patients. Method: A total of 200 pre diagnosed HCV patients were divided according to age and sex into four groups and monitored during their treatment period. The enrolled patients were orally treated with 400 mg/d of sofosbuvir for 12 weeks and observed after the end of treatment. Sera were separated and used for estimation of total protein, albumin, liver and kidney functions, glucose, MDA, SOD and NO. Results: the treated patients with sofosbuvir showed significant physiological changes, including high elevation of liver functions at the beginning of the treatment course that gradually decreased with time. Highly significant elevation in the glucose and creatinine levels were reported in the old age groups (male and female). Uric acid showed significant elevation in the male groups. However, MDA and NO were significantly increase in all patients group except for NO level in the old female group. Meanwhile SOD act differently and elevated in the females studied groups. Conclusion: It could be concluded that the use of recent multi-targeted regimen Sofosbuvir in HCV treatment has some effects on liver and kidney functions as well as on many oxidant/ antioxidant parameters. Therefore, further detailed studies are required with special attention for the differences in age and sex.