It has been projected that ferritin and iron yoke in homozygous thalassemic children is coupled with the enhanced free radical formation and blemished in antioxidative defense coordination. Aim: The purpose of the current study was to analyze the consequence of serum iron, erythrocyte catalase, and erythrocyte superoxide dismutase (ESOD) in patients with beta-thalassemia major. Method: 60 beta-thalassemia major patients were studied before and after supplementation of A – Z antioxidants for 20 weeks, and status were compared with 60 age and sex-matched healthy normal. Serum Iron estimation was carried out by Ramsay’s Dipyridyl Method. Estimation of erythrocyte superoxide dismutase was done by Kajari Das Method. The levels of Catalase concentration in erythrocytes were analyzed by the Goth method. All the objectives mentioned above were run by using a UV visible Spectrophotometer (Systronix). Results: A marked enhancement was seen in the intensity of serum iron, and superoxide dismutase (p<0.001) with parallel decline was observed in the level of erythrocyte catalase (p<0.001) in homozygous thalassemia patients when compared with healthy subjects. After 20 weeks of regular supplementation of antioxidants A-Z syrup, which consists of multimineral multivitamins, the concentration of catalase was increased whereas iron and ESOD (p<0.001) were reduced significantly when compared with normal and baselines thalassemic patients. Conclusion: Due to multiple blood transfusions, beta-thalassemia major children are at advanced risk due to secondary iron surplus and intense oxidative stress. Such kind of circumstances may be handled with supplementation of antioxidants A-Z syrup with their regular treatment.