Background: Early identification of neonatal infection is, however, a major diagnostic problem due to presence of non specific clinical signs and limitation of current diagnostic procedures. Objective: Making a comparison of the accuracy of neutrophil cluster of differentiation 64 (CD 64) versus
C -  reactive  protein (CRP) as a single test for the early detection of neonatal sepsis. Patients and Methods: A prospective study enrolled newborns with proved sepsis (n=64) and control newborn (no=32). CRP, neutrophil CD64, complete blood count and blood culture were taken at the time of suspected sepsis for proved sepsis and at the time of venipuncture for labortary tests in control newborns. Neutrophil CD64 was analyzed by flowcytometry. Results: CD64 significantly elevated in the groups with proved sepsis  ,whereas CRP did not significantly increase in comparison with controls.  CD64 and CRP have sensitivity 85.9 % and 48.7 %, specificity 78.1% and 71.9%, positive predictive value of 88.7%and 77.5% and negative predictive value 73.5% and 41.1 % respectively. The area under the receiver operating characteristic curves for CD64 and CRP were 0.83 and 0.48  respectively .             Conclusion: CD64 expression on neutrophils increased significantly in neonates with neonatal sepsis. CD64 was a more specific marker for neonatal sepsis than CRP as shown by area under the curve (AUC)