Introduction: Diagnosis of sepsis is important to reduce morbidity and mortality. Leptin is an important immunoregulatory hormone that enhances a number of immune responses in sepsis. Objective: to assess serum leptin in diagnosing sepsis in critically ill pediatric patients. Subjects and Methods: This study was carried out on 50 children divided into a case group included 40 critically ill patients initially sepsis free and fulfilling 2 of 4 criteria of SIRS admitted to the Pediatric Intensive Care Unit, children hospital, Tanta university and a control group included 10 apparently healthy children. According to the presence or absence of infection, our patients were classified into SIRS group and sepsis group. For all studied patients; serum leptin, CRP and others indicators of sepsis were measured at admission and 72h later, while were measured one time only for control group. Results: patients who developed sepsis had significantly higher serum leptin levels than those of the control group and SIRS (33.9 ± 20.8 vs. 1.9 ± 0.4, 21.5+ 10.1 respectively, p>0.05). Conclusion: Serum leptin may have a role in early diagnosis of sepsis.