Objectives To investigate the effects of new antiepileptic drugs [oxcarbazepine (OXC), levetiracetam (LEV), lamotrigine (LTG)] on thyroid hormones in male adults with epilepsy. Methods Thirty-eight newly diagnosed male adult patients with epilepsy were enrolled in the Epilepsy Center of Sichuan Province People's Hospital from April 2015 to November 2016. The diagnosis was in line with the classification of epilepsy defined by the International League Against Epilepsy (ILAE, 1981). Only patients with generalized or secondary generalized epilepsy were recruited into the present study. Individual treatment with OXC, LEV, or LTG was randomly assigned to the 38 patients. Thyroid hormones was measured before treatment and 6 months after taking the medicine. Followed by an analysis of the comparison between the treated patients and healthy volunteers (healthy controls) as well as the changes and differences between the patients themselves before and after treatment. Results There was no significant difference in the thyroid hormone levels between male patients with epilepsy before taking the medicine and healthy controls (P>0.05). After 6 months, total thyroxine (TT4) and free thyroxine (FT4) in OXC group was significantly lower than the baseline (P<0.05). However, the thyroid hormone levels in the LEV group and LTG group showed no statistical difference before and after treatment (P>0.05). Conclusions OXC can reduce serum total thyroxine (TT4) and free thyroxine (FT4), which might be harmful to thyroid hormone of patients.