Background: Epilepsy is one of the most common neurological disorders. The prevalence of active epilepsy was estimated to be 6.38 per 1000 persons. Serum malondialdehyde (MDA) is used as a marker to investigate the oxidative damage of lipids in many degenerative human diseases. Vitamin C is important for the proper functioning of the central nervous system.  Objective: To evaluate the association of serum MDA and vitamin C with epilepsy in children. Methods: This case-control study was carried out in the Pediatric Department at Zagazig University Hospitals during the period from December 2019 to July 2020. This study included 46 children who were divided into 2 groups: Cases group: which included 23 epileptic children. Control group: which included 23 healthy children with age and sex-matched to cases.  All the participants were subjected to measuring serum malondialdehyde MDA and Vitamin C. Results:  This study showed that there was a statistically significant increase in serum malondialdehyde (MDA) among the case group than the control group. Also, there was a statistically significant decrease in serum Vitamin C among the case group than the control group.  Conclusion: This study has correlated the increase of lipid peroxidation and defective antioxidant defense and the pathogenesis of epilepsy and we found a significantly elevated level of MDA and a depleted level of vitamin C in epileptic patients than in the healthy control subjects