Background: Oxidative stress has been related in a wide variety of ways with nervous tissue. We studied the effect of antiepileptic monotherapy on serum level of total antioxidant capacity, lipid hydroperoxide, total peroxide, oxidative stress index, and individual serum antioxidants such as albumin, bilirubin and uric acid. Patients and Methods: We studied 122 subjects including healthy controls, untreated epileptic patients and epileptic patients treated with valproic acid, carbamazepine or phenobarbital. Serum total antioxidant capacity was measured as an index of antioxidants, and total peroxide was measured as index of oxidative stress. The serum concentrations of uric acid, albumin, bilirubin and lipid hydroperoxide were monitored simultaneously. Results: We found that serum total antioxidant capacity levels were significantly decreased in the untreated group compared with the controls. Serum total peroxide levels were markedly increased in the untreated and carbamazepine- treated groups compared to in the controls; and lipid hydroperoxide and oxidative stress index levels were significantly higher in the phenobarbital- treated group than in the controls. Uric acid concentrations were significantly lower in the valproic-acid-treated group than in the untreated group, and total bilirubin concentrations were higher in the untreated group than in the controls. Conclusion: Epileptic children exposed to oxidative stress and conventional antiepileptic drugs change the oxidative/antioxidative balance. The serum oxidant and antioxidant status of epileptic children with valproic acid monotherapy are better regulated compared with children with carbamazepine and phenobarbital monotherapy. Copyright (c) 2007 S. Karger AG, Basel.