Background: Antiseizure drug valproate alters thyroid functions. Magnesium is implicated in the pathogenesis of epilepsy and it may affect the efficacy of valproate and thyroid functions.Objective: To study the effect of six months of valproate monotherapy on thyroid functions and serum magnesium levels. To study the association among these levels and the effects of clinicodemographic profile.Materials and method: Children aged three to 12 years presenting with newly diagnosed epilepsy were enrolled. A venous blood sample was collected for estimation of thyroid function test (TFT), magnesium, and valproate levels at onset and after six months of valproate monotherapy. Valproate levels and TFT were analyzed by chemiluminescence and magnesium by colorimetric method.Results: Thyroid stimulating hormone (TSH) increased significantly from 2.14±1.64 µIU/ml at enrollment to 3.64±2.15 µIU/ml at six months (p<0.001), free thyroxine (FT4) decreased significantly (p<0.001). Serum magnesium (Mg) decreased from 2.30±0.29 mg/dl to 1.94±0.28 mg/dl (p<0.001). At six months, eight out of 45 (17.77%) participants had significantly increased mean TSH levels (p=0.008). Serum valproate levels were not associated significantly with TFT and Mg (p<0.05). There was no effect of age, sex, or repeat seizures on the measured parameters.Conclusion: The TFT and Mg levels are altered by six months of valproate monotherapy in children with epilepsy. Hence we suggest monitoring and supplementation if required.