Abstract Background: Neonatal sepsis is considered a major cause of morbidity and mortality among neonates worldwide. Pre-mature infants are more susceptible to sepsis. Diagnosis and management of sepsis are great challenges facing neonatolo-gists in NICUs. Aim of Study: The aim of this study was to evaluate the incidence of neonatal sepsis at neonatal Intensive Care Unit in Tanta University Hospital. The study was carried out on all admitted neonates with clinical signs and symptoms of sepsis at the time of admission or who developed sepsis during their hospital stay. Patients and Methods: This study was prospectively conducted over a period of 12 months from August 2017 to August 2018, at NICU in Tanta University Hospital. Results: A total of 330 neonates admitted to our TUH NICU along one year from August 2017 to August 2018 were divided into 2 groups as regard clinical and laboratory findings of sepsis. The 2 groups were: Group 1 (case): Sepsis group included (145) neonates who showed clinical presentation and laboratory findings of sepsis and Group 2 (control): Non sepsis group included (185) neonates who were free and not showing any manifestations of sepsis or any laboratory findings of sepsis. Conclusions: The incidence of neonatal sepsis in our TUH NICU was about 43.94% along one year and the most common organisms was klebsiella (31.03%) followed by staph aureus (20%).