A relationship between ghrelin and epilepsy has been already shown in humans, although the results are controversial. Ghrelin levels are reduced in obesity. Epileptic patients progressively develop a therapy-linked weight gain; however, the mechanisms for this have not been fully explained. The aim of our study is to evaluate if ghrelin secretion is modulated by treatment with carbamazepine or valproic acid in young prepubertal epileptic children. Ghrelin levels were reduced in normal-weight young epileptic prepubertal children under treatment with carbamazepine (p < 0.0001) or valproic acid (p < 0.006) compared to healthy age- and weight-matched subjects. Ghrelin was also lower in children under carbamazepine when compared to those under valproic acid (p < 0.01). A derangement in ghrelin secretion in epilepsy during specific pharmacologic therapies and independent of weight gain could be hypothesized.