Background: Overweight and obesity are common comorbidities in patients with epilepsy. The relationship between epilepsy and body weight is complex. This connection is often linked to chronic inflammatory processes. This study aims to explore the role of obesity in individuals with epilepsy and determine whether a correlation exists between the two conditions. Methods: This case-control study was carried out in the Neurology Clinic and Neurology Department, Faculty of Medicine, Zagazig University Hospitals on 224 persons categorized into two groups: patient group (112 epileptic patients who were further subdivided into two group: 52 treatment responsive group and 60 treatment nonresponsive group) and 112 control group . Both patients and control group were subjected to comprehensive evaluations, standard laboratory tests, as well as serum interleukin-6 (IL-6) levels with assessment of body mass index (BMI). Electroencephalograms, Brain MRIs were conducted to all patients. Results: The mean of BMI was significantly higher among the epilepsy patients than control group (P<0.001). patients with resistant epilepsy had higher BMI (P=0.004) in comparison to those with good response to treatment. The mean BMI was higher among generalized tonic-colonic seizures (P=0.02), patients who had a positive history of status epilepticus and those who received polytherapy (P=0.01) and (P=0.001) respectively. In addition, serum IL-6 levels are significantly elevated in overweight and obese epileptic patients (P<0.001). Conclusions: Our study concluded that high BMI has been involved in causing systemic inflammation as obesity cause an inflammatory response and elevate the level of neuroinflammatory mediators, including IL-6. Body mass index (BMI) and IL-6 are a significant independent indicator for drug-resistance among epileptic patients