Background: Millions of dead cases are reported every year due to sepsis. Sepsis has been estimated in 1-2 % of hospitalized patients especially leukemic patients. The diagnosis of sepsis remains a clinical challenge. Many studies suggest that presepsin plays a role in diagnosing sepsis, but the results remain controversial. Objective: To evaluate the potential of presepsin as an early biochemical marker of sepsis in adult acute leukemic patients and to assess the correlation between severity of sepsis and level of presepsin. Comparing between presepsin & CRP in diagnosing bacterial infection in critically ill adult leukemic patients. Patients and Methods: This study was conducted on 24 patients having acute leukemia after receiving chemotherapy and 24 controls at Medical Oncology and Clinical Pathology Departments, Zagazig University Hospitals during the period from June 2018 to August 2019. Results: There was statistically significant difference between patients and control regarding presepsin levels. The highest levels of presepsin were in patients with septic shock followed by severe sepsis, sepsis, SIRS then control group. There was statistically significant difference between types of sepsis and presepsin (P value = 0.000). There was statistically significant positive correlation between CRP and presepsin (r = 0.658). AT cut off value of 440 the clinical sensitivity of presepsin was 82.5% and its clinical specificity was 90%, AUC was 0.89. On comparing these results with the normal cut off value of CRP level (6), the clinical sensitivity and specificity were 90% & 61% respectively and AUC was 0.70. Conclusion: Presepsin can be used as a better indicator to the degree of severity of sepsis than CRP in septic adult leukemic patients.