Background: The immune system has been a hotspot for epilepsy researchers during the past decade. The outcome of this is an everincreasing body of knowledge about the role of several immunological variables in the development of epilepsy and seizures epileptogenesis. Methods: We carried out this case-control study in the Neurology Clinic and Neurology Department, Faculty of Medicine, Zagazig University Hospitals,on 224 persons categorized into two groups: 112 epileptics and 112 controls. Comprehensive evaluations were conducted on all patients, including electroencephalograms, brain MRIs, standard laboratory tests, as well as serum interleukin-6 (IL- 6) levels that were assessed by an enzyme-linked immunosorbent assay (ELISA). Results: Patients with epilepsy had a significantly elevated serum IL-6 level compared to the control group (P<0.001). A statistically significant difference was detected between drug-responsive and drug-non-responsive patients as regard IL-6, as the mean level of IL-6 was higher among drug-non-responsive patients (P=0.02).Also, IL-6 level was significantly higher among patients with generalized tonic-clonic seizures (P=0.02). The median level of IL-6 was significantly higher among patients who received polytherapy compared with those on monotherapy (P=0.001). Also, the median IL-6 level was significantly higher among patients who had generalized epileptiform activity compared with those who had partial-onset seizures(P=0.01). Conclusions: The correlation between serum IL-6 levels and epilepsy was statistically significant. Epileptic seizures could induce the production of IL-6, and a high concentration of IL-6 could be an obvious neurotoxic and pro convulsion factor