Objective To determine the changes in thyroid function tests in children who underwent antiepileptic therapy in Shahid Beheshti Hospital, Kashan, in 2008. Materials & Methods This analytical-observational study was carried out in a cohort fashion without an external control group (self controlled) on 45 children with new onset epilepsy who had not been previously treated with antiepileptic medications. Three subjects were excluded from the study because of presenting clinical symptoms of hypothyroidism. Plasma levels of TSH, T3, FT3, T4 and FT4 hormones were measured and compared at baseline and 3 and 6 months after treatment. Results The results of Mann-Whitney statistical analysis suggested that the increase in the plasma level of TSH was significant only in the Sodium Valproate group. The plasma level of T3 significantly decreased 3 and 6 months after treatment in the Phenobarbital group while the plasma level of FT3 significantly decreased only in the Sodium Valproate group. The decrease in T4 plasma level was significant in all groups (Carbamazepine group, Sodium Valproate group and Phenobarbital group) 3 and 6 months after the onset of treatment but the decreasing in FT4 plasma level was only significant in the Carbamazepine group 6 months after the commencement of treatment. Conclusion Phenobarbital had the least effect on thyroid hormones. Considering the effect of such medications on thyroid function tests, it seems necessary to check the plasma levels of hormones periodically after beginning the treatment