BACKGROUND The phenotypic expression of sickle cell disease (SCD) is a complex pathophysiologic condition. However, sickle erythrocytes might be the cause for multiple sources of pro-oxidant processes with consequent linked to chronic and systemic oxidative stress. Herein, we explored the SCD phenomena could be the result in formation of oxidative stress as well as inflammation in children. METHODS Blood samples of 147 SCD subjects were evaluated. A control group was formed of 156 individuals without SCD. Different oxidative stress markers and inflammatory mediators were measured by using various biochemical techniques. Plasma samples were collected from blood for the measurement of antioxidants and reactive oxygen species (ROS). RESULTS The levels of plasma hydroxyl radical (HO•), and nitric oxide (NO) production were higher in SCD children in compared to control groups. The plasma antioxidants capacities such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and protein thiol levels were significantly reduced in SCD children. The plasma lipid peroxidation, protein carbonylation, DNA damage markers were significantly altered in different age groups of SCD children. Further, our results showed that SCD children have chronic inflammatory disease due to persistent alteration of haemoglobin content, reticulocyte, total bilirubin, platelet, creatinine, leukocytes, and altered expression of inflammatory mediators in compared to control groups. CONCLUSIONS SCD children have high oxidative stress, and conversely, decreased antioxidant activity. Decrease in antioxidant activity might explained the reduction in lipid peroxidation, protein carbonylation and increased inflammation, which in turn intensify the symptoms of SCD in children.