Background:  Despite recent advances in neonatal care, sepsis remains a worldwide leading cause of morbidity, mortality and prolonged hospital stay in NICUs, so that the accurate and early diagnosis of neonatal sepsis is a relevant problem. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Therefore, calprotectin has been proposed for the diagnosis of inflammatory conditions. Objective: This study aimed to evaluate the diagnostic value of serum Calprotectin in newborns with suspected sepsis.    Methods: This case control study comprised 40 neonates, 20 neonates with suspected clinical sepsis and other 20 healthy neonates with no clinical signs of sepsis as a control group. Serum level of calprotectin was measured for all neonates recruited in this study, by a commercial ELISA assay     Results: Among the cases group, a total of 15 neonates (75%) had positive blood culture. Serum calprotectin levels were significantly higher in septic group than non- septic and control groups as mean Serum Calprotectin was 2.5±0.95  μg/ml, 1.58±0.25 μg/ml and 1.01±0.29 μg/ml, respectively.     Significant positive correlations were found between calprotectin levels and WBCs and IM ratio, while negative correlations were found between its level and lymphocytes and platelets. In our study, Calprotectin sensitivity and specificity values were 92% and 93.3%, respectively. Conclusion: Serum calprotectin levels were significantly higher in neonates with sepsis. Its levels correlated well with other laboratory markers of sepsis and neonatal mortality. It is a sensitive diagnostic marker for neonatal sepsis.