Background: thalassemic patients with frequent blood transfusion can result in iron overload and increase serum ferritine level. Leptin is a polypeptide hormone that is mainly expressed in bone marrow and adipocytes and previous studies consumed that it is lower in thalassemic patients compared to healthy children as a result of hemsedrosis. Objectives: The aim of this study was to evaluate leptin serum levels in patients with β- thalassemia major. Patients and methods:  This case-control study was conducted on 50 children from 13 to 17 years old, at Al-Azhar university Hospitals (Sayed Galal & Al-Hussien hospitals). They were subdivided  in  two  groups  30  patients (ß- thalassemia major)  and  20  as  control that  were  matched  in  age  and  sex. All  Children were examined to be free from heart disease , iron  deficiency  anemia,  kidney  disease,  diabetes,  fever  and  systemic  diseases  were enrolled after taking informed consent of their parents. After collecting the samples, leptin and ferritin levels of the serum were measured in two groups by ELISA method. Then, the data were analyzed by the related statistical tests and SPSS 20 software. Results: The  mean  of  the  serum  levels  of  leptin and  ferritin  showed  a  significant difference in the case and control groups (P-value < 0.05). Levels of leptin in the case group showed no significant gender difference (P-value < 0.05). Conclusion: Based  on  the  results  of  this  study, thalassemia  major reduces  serum  levels of  leptin regardless of age and body mass.