OBJECTIVES: Recently, inflammation have been proposed as one of the mechanisms underlying the patology of drug-resistant epilepsy (DRE). Ketogenic diet (KD) is one of the therapeutic methods used in DRE. There are some data that adipokines may modulate inflammatory processes and their concentrations are influenced by KD. Therefore, the aim of this study was to evaluate the influence of KD on serum leptin, chemerin and resistin in children with DRE. DESIGN: A cross-sectional observational study performed on 72 subjects aged 3-9 years, divided into 3 groups: 24 children with DRE treated with KD, 26 treated with valproic acid (VPA), and a control group of 22 children. MATERIAL AND METHODS: Anthropometric measurements (weight, heigth, BMI, waist to hip circumerences ratio) were performed in all participants. Biochemical tests included serum fasting glucose, insulin, beta-hydroxybutyric acid, lipid profile, alanine aminotransferase and aspartate aminotransferase activities and blood gasometry. Serum levels of leptin, chemerin and resistin were assayed using commercially available ELISA tests. RESULTS: Serum levels of leptin and chemerin in the KD group were significantly lower and resistin - higher in comparison to patients receiving VPA and the control group. In children treated with the KD, leptin concentrations correlate with insulin levels and HOMA-IR scores. Chemerin levels in this group, in contrast, show negative correlation with body mass and height expressed as standard deviation scores from the mean for age and sex. CONCLUSIONS: Modification of pro-inflammatory adipocytokine levels is potentially one of the mechanisms of anticonvulsant effects of KD in children with refractory epilepsy.