The present study is undertaken to demonstrate the oxidant-antioxidant status including serum lipid peroxidation product malondialdehyde (MDA), serum total antioxidant capacity (TAC), paraoxonase (PON), tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in Egyptian children with sickle cell anemia. Thus, the levels of MDA, TAC, PON, and TNF-α and VEGF were measured in 52 children with homozygous sickle cell anemia (30 males and 22 females) and 25 healthy age- and gender matched controls. The present results markedly declared significant elevated serum MDA level, while, serum AC and paraoxonase levels were significantly reduced in children with SCA as compared to control subject. On the other hand, cytokines levels, TNF-–α and VEGF levels were elevated significantly (P≤0.01) in SCA children as compared to normal control group. .There were significant change in the levels of MDA, TAC, PON, and TNF-α and VEGF were detected in sickle cell patients treated with hydroxyurea (HU) as related to untreated one. It was found that MDA level was found to be independent on PON and TAC. Also, an insignificant relationship were detected between serum MDA, TAC, PON and TNF-α and VEGF levels. Thus, it could be concluded that, the steady state between oxidant and antioxidant declaring the chronic oxidative stress, increased VOC frequency, decrease in PON level as well as increase cytokine levels in these patient.