Background: Oxidative stress is fundamental in initiating pathophysiological mechanisms leading to premature hemolysis resulting in iron overload in patients with beta thalassemia. Peroxiredoxin 2 (Prdx2) is one of the crucial cytoprotective and antioxidant systems that play a key role against oxidation. Our aim was to investigate serum Prdx2 levels in children with beta-thalassemia and to explore its possible relations with iron overload. Methods: The patients were divided into two groups: beta thalassemia major (BTM) group (n=40) and beta thalassemia intermedia (BTI) group (n=20). To compare serum Prdx2 and iron status parameters levels, a control group (n=20) was include in the study. Serum Prdx2 levels were determined by enzyme linked immunosorbent assay technique. Serum levels of iron and ferritin were measured using automated chemistry analyzer and electrochemiluminescence immunoassay respectively. Results: Serum Prdx2 concentrations in thalassemia major patients were significantly lower than those in thalassemia intermedia patients (P= 0.026); and Prdx2 concentrations in thalassemia intermedia patients were significantly lower than those in control group (P<0.001). In both thalassemia major and intermedia groups, serum Prdx2 concentration was positively correlated with serum iron (r = 0.558, P=0.002; r = 0.718, P=0.004, respectively) and ferritin levels (r = 0.422, P=0.007; r = 0.550, P=0.012, respectively). Conclusions: Our results demonstrate the positive association between Prdx2 and iron overload in thalassaemia patients. These findings may suggest unconventional therapeutic approach to control consequences of iron overload through modification of Prx2 activity.