Background: Sickle cell anemia is the most common hematological monogenic, inherited disease in the world. It is due to point mutation at position 6 in the beta- globin gene that gives rise to an abnormal hemoglobin molecule (HbS) with higher potential for oxidative damage. Oxidative stress can be defined as a condition in which the balance between the generation of oxygen free radicals (reactive oxygen species) (ROS) and the antioxidant defenses is disturbed to such an extent that it results in impairment of cellular function, Sources of ROS are either intracellular, extracellular or both. Objectives: The current study aimed at evaluating oxidative status of children with sickle cell anemia, through estimating the level of plasma lipid peroxidation product malondialdehyde (MDA) and total antioxidant capacity in these patients. Methods: This study included forty patients with established diagnosis of SCA in Steady state disease. Further 20 apparently healthy subjects with matching age & sex were included and served as a control group. Plasma malondialdehyde, plasma paraoxonase,plasma nitric oxide and Total antioxidant, were estimated calorimetrically. Results: Plasma MDA level was significantly higher (P< 0.0001) in SCD cases compared to controls and the mean total antioxidants level, vitamin E, NO and paraoxonase were significantly lower among SCD patients compared to controls (p<0.05). No significant differences in the mean level of NO, paraoxonase and TAO and MDA in SCD males when compared with SCD females (P˃ 0.05). No significant differences in the mean level of NO, paraoxonase and TAO and MDA in SCD cases on HU when compared with SCD cases not receiving HU (P˃ 0.05). For the Cut-off values of antioxidant enzymes for prediction of occurrence of VOCs whatever its frequency we found that area under the curve of NO was 0.782 versus 0.701 for paraoxonase and 0.650 for TAO and this difference was statistically significant (p=0.006). Conclusions: Increased level of lipid peroxidatation product MDA was found in SCD patients accompanied with significantly lower activity level of antioxidant enzymes indicates that SCA patients produced greater quantities of reactive oxygen species formed by sickle erythrocytes which are less likely to be removed effectively with the endogenous mechanism.