Objectives: This work was carried out to evaluate the relation between the anemia of chronic renal failure (CRF) and glutathione system through measurement of the reduced and oxidized forms of glutathione (GSH and GSSG respectively). Methods: RBCs and plasma of 30 children suffering from CRF: 20 on hemodialysis (HD) and 10 treated conservatively were compared to 10 normal controls. Results: CRF patients had their mean RBCs GSH significantly lower and plasma GSSG significantly higher than controls. This could be the result of reduced activity of glutathione reductase enzyme or its overexhaustion in detoxifying oxidants presents in uremic blood. GSSG was significantly lower in uremic RBCs as it can readily pass through the RBCs membrane. No differences were observed among patients under HD and those treated conservatively. Erythropoietin therapy had a beneficial effect on glutathione system through raising RBCs GSH. Vitamin E supplementation induced significant decrease in frequency of blood transfusions. Conclusions: Uremic children are exposed to oxidative stress that could affect the survival of RBCs. HD does not pose an extra-burden on glutathione system. Every attempt must be made to keep this system in an optimal state possibly through vitamin E and selenium supplementation.