Purpose: Febrile seizures (FS) are seizures that occur between the age of 6 and 60 months, but its pathophysiology still is not fully understood. There is limited information about the correlation between levels of selenium and leptin with FS. This study aimed to determine the relationship between serum levels of selenium and leptin in children with FS. Methods: This case-control study was conducted in a University Hospital in Shahrekord, Iran, in 2011. The serum levels of selenium and leptin of 25 children with simple febrile seizure (case group) were compared with 25 febrile children without seizure (control group) in acute phase and after three months. The levels of serum selenium and leptin were measured by flame atomic absorption spectrophotometer and enzyme-linked immunosorbent assay method, respectively. Results: In acute phase, the mean serum level of selenium in case and control groups were $95.88{pm}42.55$ and $113.25{pm}54.43{mu}g/dL$, respectively, and difference was not significant (P=0.415), but after three months, this level had a significant increase in both groups (P<0.001). In acute phase, the mean serum leptin level in case and control groups were $0.94{pm}0.5$ and $0.98{pm}0.84$ ng/mL, respectively, but difference was not significant (P=0.405). After three months, serum leptin level had no significant change in both groups (P=0.882). Conclusion: These observations suggest that serum levels of selenium and leptin have not specific relation with FS but overllay is lower, however, further study is recommended. Also selenium level in stress and acute phase was significantly lower than recovery phase.