Bacterial infections is a major cause of neonatal morbidity and mortality. This work was conducted in order to assess the role of exchange transfusion in neonatal sepsis especially in the critically ill neonate. The study was conducted on 126 neonates with proven sepsis over one year (2000) admitted to NICU At Kasr Aini Hospital. Patients were subdivided into 2 groups. The first group (Antibiotic group) included 93 neonates treated by antibiotics only. The second group (Exchange group) included 33 neonates who were treated by antibiotics and exchange transfusion. In the 2nd group the discharge rate was 39.4%, mortality rate was 60.6% (<0.001), while in the 1st group 80.6% were discharged and 19.4% died (0.001). This study concluded that the use of exchange transfusion in the treatment of neonatal sepsis does not improve the outcome of disease. It also increases the mortality rate.