The study was designed as a trial to define etiological relationship between growth regulating cytokines and failure to thrive in children with congenital heart diseases (CHD) and included 20 children (12 males and 8 females, with age range 2-6 years) having CHD and 10 healthy as a control. Patients were subjected to clinical examination to determine their anthropometric measures and were investigated using plain X-ray chest, electrocardiogram (ECG) and echocardiography to verify the type of CHD. Serum fasting levels of insulin, insulin-like growth factor binding protein-3 (IGFBP-3) were estimated by radioimmunoassay and serum leptin by quantitative enzyme immunoassay (ELISA). There were 8 (40%) patients with cyanotic CHD, all had Fallot's tetralogy (F4) and 12 (60%) patients with acyanotic CHD. Patients showed a significant decrease (P<0.05) in weight compared to controls. Serum insulin and IGFBP-3 showed a significant decrease (P<0.05) in patients compared to control levels with a non-significant difference between cyanotic and acyanotic patients. The 24-hr mean serum leptin showed a non-significant increase in patients compared to controls, with a non-significant increase in acyanotic compared to cyanotic patients. PM Serum leptin was significantly increased (P<0.05) compared to AM levels, whether in control or patient samples. Furthermore, there was a positive significant correlation between weights of children, whether control or patients and serum levels of both insulin and IGFBP-3, while there was a negative significant correlation between weight and the mean of 24-hr serum leptin in both groups. Moreover, there was a negative significant correlation between serum leptin and serum levels of both insulin and IGFBP-3, in both groups. We speculate that the decreased ability to thrive in children with CHD could be attributed to decreased insulin and IGFs secondary to increased leptin levels in these children.