Introduction: Neonatal sepsis represents a major health problem with high mortality and morbidity rates. Although early diagnosis of neonatal sepsis is very important for proper management yet it remains a difficult task. Neutrophil CD64 (nCD64) is used as a marker for the diagnosis of sepsis, requiring a small sample volume, short turnaround time. Objectives: In this study we aimed to study the diagnostic performance of nCD64 against routine markers in low birth weight neonates (LBWN) with sepsis. Patients and methods: A case control study was conducted on 40 LBWN suspected clinically to have early onset neonatal sepsis against 20 neonates clinically free of sepsis as control. Investigations included CBC, CRP, blood culture andnCD64 expression. Results: among the studied markers of sepsis; immature neutrophil count, immature /mature ratio, immature/total ratio, CRP and nCD64 were significantly higher in suspected group than control (p value 0.007, 0.001, 0.002, 0.001, and 0.001 respectively). Among the group of neonates with suspected sepsis, blood culture of 11 cases (27.5%) did not show growth. nCD64 showed the highest sensitivity and specificity; 100% each. Immature neutrophil count and total leucocytic count showed the lowest sensitivity 40% and mature neutrophil showed the lowest specificity 45%. The expression of nCD64 in those neonates who died as a complication of sepsis was significantly higher than those who survived (p value 0.001). Conclusion: nCD64 is a reliable marker for the diagnosis of early onset neonatal sepsis in LBWN with a significant predictive value for disease course.