Background and study aim:: Combined anti-hepatitis C therapy with pegylated interferon and ribavirin is associated with numerous side effects that affect both patients' compliance and response rates. These side effects are believed to be, in part, due to oxidative stress induced by ribavirin. In the present work, we tried to evaluate if antioxidants can ameliorate the side effects of this therapy in patients with chronic hepatitis C (CHC). Patients and methods: Two hundred selected patients with CHC were randomized to receive either the standard antiviral combination therapy (Peginterferon and Ribavirin) plus antioxidant mixture (slow release vitamin C 500 mg daily, vitamin E 400 mg daily, silymarin 420 mg daily and N-acetylcystein 600 mg daily) for 48 weeks (study group, group I) or to receive the standard combination therapy only for 48 weeks (control group, group II). Patients were followed up during the whole treatment course to assess the occurrence of subjective and laboratory side effects of the combined antiviral therapy. Results :The results of our study revealed statistically significant difference between both groups regarding changes in hemoglobin concentration along therapy from week one onwards as reduction in hemoglobin concentration along therapy was significantly lower in group I; p = 0.001. The frequency of significant anemia (Hb < 10 gm/dl) in group I was significantly lower than Group II from week twelve onwards; p value ranged from 0.013 to 0.001. Moreover, the frequency of fatigue was significantly lower in group I from week two onwards till the end of therapy; p value ranged from 0.027 to < 0.001. On the other hand, all other checked side effects either subjective or laboratory revealed a non significant statistical difference between both groups. Conclusion : The use of an antioxidant mixture with antiviral combination therapy in patients with CHC can improve treatment associated anemia and fatigue but has no effect on other treatment associated side effects.