BACKGROUND Epilepsy is one of the most common neurological diseases in childhood and adolescence. Carbamazepine (CBZ) and valproate (VPA) have been widely used as the first generation of antiepileptic drugs (AED). OBJECTIVE The aim of the study has been to evaluate and compare the effect of CBZ and VPA monotherapy on aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) serum levels in children. METHODS The study has included 100 patients (boys 57/girls 43, age range 1 to 18 years), who have been treated with CBZ or VPA, as initial monotherapy, for at least 12 months. Patients with liver lesions or patients who have been treated with other drugs have been excluded from the study. The initial serum enzyme levels (AST, ALT and GGT) and after 12 months of treatment have been compared. RESULTS 53/100 (53%) patients have been treated with CBZ and 47/100 (47%) patients have been treated with VPA.The initial level of enzymes were within the referece range. After one year-long treatment AST was elevated at 4/53 (7.5%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =3.965, p<0.05). ALT was elevated at 5/53 (9.4%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =6.953, p<0.05). GGT was elevated at 18/53 (34%) CBZ patients and 7/47 (14.9%) VPA patients (x2 test =4.831, p<0.05). CONCLUSIONS The levels of enzymes AST and ALT have been elevated statistically significant in VPA group and GGT in CBZ group.