Background Free radicals’ excessive production contributes to increasing the burden of oxidative stress in critically ill patients. This could be involved in the pathogenesis of tissue damage and systemic dysfunction. In this study we aimed to assess the oxidative stress status through evaluation of oxidants and antioxidants levels in critically ill pediatric patients. Methods This study included 25 pediatric ICU critically ill patients; and 25 healthy age and sex matched controls. Patients were subjected to detailed medical history and clinical examination. The degree of critical illness was assessed according to qSOFA score. Laboratory investigations included complete blood count, blood culture, serum malondialdehyde (MDA) as an index of lipid peroxidation, serum total antioxidant capacity (TAC) and paraoxonase-1 serum level as an index of antioxidants level. The comparisons were done using Independent t-test, Mann-Whitney test and One Way ANOVA. The correlations were done by Spearman correlation coefficients. Receiver operating characteristic curve (ROC) was used to detect the predictive values and area under the curve (AUC) of the studied markers Results statistically significant elevation in the level of serum MDA and TAC were detected in patients than controls (p < 0.001) for each, and decrease in serum paraoxonase-1 in cases than the controls (p < 0.001). TAC was significantly increased in patients with septic shock (p < 0.05). Positive significant correlation was found between MDA and AST (p < 0.05), TAC and AST (p < 0.01) and TAC and INR (p < 0.05). Serum MDA predicts oxidative damage with sensitivity of 80%, specificity of 68%, serum paroxonase-1 with sensitivity of 80%, specificity of 68% and TAC sensitivity of 96%, specificity of 68% Conclusion Serum malondialdehyde and paraoxonase-1 can be used as a potential biomarkers for oxidative damage of critical illness in children with good sensitivity but low specificity, while TAC can also be used as a predictor for severity of illness in children. Therefore, change of the oxidative stress and anti-oxidant status could be a possible goal for therapy in critical illness.