Background: Neonatal sepsis is a systemic condition involving hemodynamic changes and clinical manifestations caused by bacterial, viral, or fungal infection that occurs within the first 28 days of life. This study aimed to assess the accuracy of Presepsin for diagnosis and early detection of sepsis and septic shock among preterm neonates. Methods: This Cross-sectional study included 75 preterm neonates with symptoms suspicious of sepsis. The classified into 3 groups: Group 1: Infection (suspected infection not meeting the criteria for sepsis). Group 2: Sepsis (neonatal systemic inflammatory response syndrome, SIRS, plus suspected or proven infection). Group 3: Septic shock (sepsis plus cardiovascular organ dysfunction). Detailed history, clinical examination, laboratory investigations: Complete blood picture (CBC), C-Reactive Protein (CRP), blood culture and determination of Human Presepsin level in the Blood (PSEP). Results: Presepsin level was significantly lower at D3 and D5 compared to D1 (P