Background: Globally, neonatal sepsis is a prominent cause of death, particularly among preterm infants. Since sepsis biomarkers sensitivity in preterm neonates, predicting the risk of sepsis still not have been identified. So, there is a need to estimate the efficacy of multiple new biomarkers. Aim of Study: To estimate the efficacy of serum calprotec-tin in the first 2 days of life as a predictive marker for late onset sepsis in preterm neonates. Patients and Methods: The type of the research was pro-spective cohort research, performed on 40 preterm neonates without clinical and laboratory evidence of sepsis admitted at Neonatal Intensive Care Unit of Children's Hospital of Ain Shams University throughout the duration from January to June 2023 in their first 2 days of life with following-up of these ne-onates to differentiate septic and non-septic ones later on, The Research Ethics Committee approved the study, the approval number was MS 587/2022. Results: Septic neonates had statistically significant low-er serum calportectin level during their first 2 days of life and ROC Curve demonstrated that cutoff level of serum calpor-tectin that predict neonatal late onset sepsis was ≤114.2ng/ml with sensitivity & specificity of 100% for each and Area Under Curve (AUC) of 1,000. Conclusion: Serum calportectin level could be used as an early promising biomarker to predict late onset neonatal sepsis.