Sickle cell anemia (SCA) is an inherited disorder of hemoglobin synthesis, characterized bylife long severe hemolytic anemia and vaso- occlusive crisis (VOC). Oxidative stress play important role in pathophysiology of sickle cell anaemia. Therefore, 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 vaso -endothelial growth factor (VEGF) in Egyptian children with sickle cell anemia. Thus, serum levels of MDA, TAC, PON, and TNF-α and VEGF were measured in 52 steady state children with homozygous sickle cell anemia (30 males and 22 females) and 25 apparently healthy age- and gender matched controls. The present results markedly declared , significant elevated serum MDA level, while, serum TAC and paraoxonase levels were significantly reduced in children with SCA patients 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. Significant differences in mean levels of MDA , TAC, PON, TNF-α and VEGF were detected in sickle cell anemia patients treated with hydroxyurea (HU) as compared to untreated one . A significant negative correlation between PON level was found to be positively correlated with patients’ weight and BMI (r =−0.3, p = 0.02; r =−0.8, p < .001, respectively), but not with frequency of VOC. The area under the curve of serum PON in predicting occurrence of VOC was0.722 and 0.650 for TAC (p = 0.007). Serum MDA was not correlated with, PON and TAC. No significant correlations were detected between serum MDA, TAC , PON and TNF-α and VEGF levels . Thus ,it could be concluded that , these observations provide the evidence of imbalance between oxidant and antioxidant status leading to chronic oxidative stress associated with increased VOC frequency, decrease in PON level as well as increase cytokine levels in these patients, which is an interesting element need further study.