Abstract: Antiepileptic therapy is associated with alteration of thyroid hormone levels. We evaluated the effect of valproate and carbamazepine therapy on the thyroid hormone profile of epileptic children. Subjects included children aged 2-12 years receiving therapy for at least 6 months. Free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured by electrochemiluminescent assay in 30 children receiving carbamazepine, 34 children receiving valproate, and 30 age- and sex-matched control subjects. Groups were similar for age, body mass index, and duration of therapy. Thyroid-stimulating hormone (mean ± S.D.) was 2.67 ± 1.66, 4.53 ± 1.9, and 3.61 ± 1.75 μIU/mL in the control, valproate, and carbamazepine group, respectively (P < 0.001). Free thyroxine was 1.39 ± 0.19, 1.40 ± 0.63, 1.11 ± 0.19 ng/dL (P = 0.009). Free triiodothyronine was 4.03 ± 0.74, 4.14 ± 0.94, 3.92 ± 0.68 pg/mL (P = 0.54). When groups were compared 2 at a time, there was no difference in free triiodothyronine (P > 0.05). Free thyroxine levels in the carbamazepine group were significantly different from valproate (P = 0.015) and control (P = 0.027). Thyroid-stimulating hormone increased with both valproate and carbamazepine compared to control but was significant with valproate (P < 0.001). We conclude that carbamazepine and valproate therapy alters thyroid functions by decreasing free thyroxine levels. Compensation by increase in thyroid-stimulating hormone is better with valproate. The need for monitoring and supplementation should be assessed further.