β-Thalassemia (β-thal) is associated with abnormal synthesis of hemoglobin (Hb). Repeated blood transfusions in patients with β-thal major (β-TM) leads to an enhanced generation of reactive oxygen species (ROS), and subjects patients to peroxidative injury. We studied the antioxidant status and oxidative damage to children with β-thal in Jordan. Samples from 40 children with β-thal and 40 healthy controls were used. All children were under 13 years of age. Our results showed that plasma thiobarbituric acid reactive substances (TBARS) were elevated in β-thalassemic children compared to controls together with compensatory increase in superoxide dismutase (SOD) activity and decrease in catalase (CAT) activity. Elevated serum ferritin showed positive correlation with elevated liver enzyme levels except gamma glutamyl transferase (GGT), confirming liver involvement due to iron overload. Serum ferritin also showed a positive correlation with elevated TBARS and SOD, suggesting that iron overload is involved in the oxidative stress shown in cells.