Background: Thepathogenesis of febrile seizure (FS), the most prevalent convulsive condition in children under the age of five, has not been fully determined. Objective: The aim of the current study is to evaluate serum levels of adiponectin and leptin in children with FS. Patients and methods: A case-control study was conducted at the Departments of Pediatrics and Clinical Pathology of Sohag University Hospital,and included 3 groups of 30 children per group: FS, febrile controls (FC), and healthy controls (HC). Serum levels of adiponectin and leptin were measured during the acute phase using human enzyme-linked immunosorbent assay. A multivariate logistic regression analysis was conducted to study independent factors associated with FS. Results: Both the FS and FC groups had comparable serum adiponectin (median 43.5 [IQR 40-63] vs. 44 [39-83] μg/L, p < /em> 0.756) and leptin (86 [56-99] vs. 78.5 [44-111], p < /em> 0.779) levels, but both groups had significantly higher adiponectin (p < /em> 0.002, 0.003) and lower leptin (p < /em> 0.007, 0.002) levels compared with the HC group. The FS group had significantly higher body temperature on admission, WBCs, CRP, and creatinine but lower hemoglobin levels. However, in the multivariate logistic regression model, only higher body temperature on admission retained statistical significance (p < /em> 0.006). Conclusion: Serum adiponectin and leptin levels had no significant associations with FS, but this should be confirmed by larger and more comprehensive studies.