Background: Sepsis is a serious inflammatory condition caused by infection, accompanied by high morbidity and mortality. An early effective diagnostic and predictive tool is needed to improve the management and prognosis of patients. Objectives: This study was aimed to assess the role of serum levels of Heparin Binding Protein in early detection of sepsis and circulatory failure in critically ill patients, compared with the currently used biomarkers. Subjects and methods: This is a cross-sectional study of 66 patients with sepsis, carried out in emergency ICU and surgical ICU in Zagazig University Hospitals. Patients’ data were collected at admission, after 48 and 72 hours from medical records, bedside sheets, and radiographic reports. The concentration of heparin Binding Protein (HBP) is determined and compared to that of procalcitonin (PCT(, lactate, and total leucocytic count. Results: Median range level of HBP in sepsis (11.8, 9.8 and 8.083 ng/ml), septic shock (20, 22.6 and 19.25 ng/ml), and in uncomplicated infections (1.57, 0.9 and 7.3 ng/ml) on admission, after 48 and 72 hours respectively. HBP had 90.3% sensitivity, 62.9% specificity and 75.8% accuracy at cut of value ≥13.35 ng/ml AUC= 0.822, in diagnosis of septic shock on admission. Conclusion: serum heparin binding protein level is positively correlated with the severity of sepsis and septic shock and showed a good performance as an early diagnostic marker in patients with suspected sepsis and septic shock