Objectives: Weight gain and obesity are also among the side effects of long-term valproate treatment, whose etiology remains unclear. The aim of this study is to investigate the relationship between weight gain, serum neuropeptide Y and ghrelin levels in children taking valproate treatment.Patients and Methods: Our study included 25 epileptic children (14 males, 11 females; mean age 7.7±3.8 years; range 4 to 12 years) who were taking only valproate monotherapy at the outpatient clinics. All study participants were analyzed in terms of body mass index, serum neuropeptide Y and ghrelin levels before treatment and after a follow-up period of one year.Results: At the end of follow-up, the mean body mass index measurements increased, whereas the mean serum neuropeptide Y and ghrelin levels decreased; twelve patients (48%) gained obesity.Conclusion: This study demonstrated low serum ghrelin and neuropeptide Y levels in children receiving valproate treatment. New studies with larger sample sizes and longer follow-up periods are needed to evaluate the mechanism of weight gain due to valproate treatment in this population.