Sepsis in neonates hospitalized in the NICU is a global problem and is a significant contributor to morbidity and death. The clinical signs are non-specific and indistinguishable from those caused by a variety of neonatal noninfectious disorders.Early recognition and diagnosis of neonatal sepsis are difficult but is extremely important because prompt institution of antimicrobial therapy improves outcomes. Isolation of bacteria from a central body fluid (usually blood) is the gold standard and most-specific method to diagnose neonatal sepsis. Neutrophil surface CD64, the high-affinity Fc receptor, is quantitatively upregulated during infection and sepsis, under the influence of inflammatory cytokines; this increase occurs in a graded manner dependent on the intensity of the cytokine stimulus, and CD64 expression is stable for >24 hours. Technological advances in flow cytometry have made it possible to quantitate neutrophil CD64 rapidly, with precision, and with minimal blood volumes.