Abstract Background: Sepsis is a type of systematic inflammatory response syndrome caused by invasion of pathogens or con-ditional pathogenic bacteria into the blood circulation. Aim of Study: To evaluate the value of the presepsin in early diagnosis of sepsis in comparison with procalcitonin (PCT) and assess prognostic significance of presepsin in sepsis evaluation in relation with PCT. Patients and Methods: A prospective cohort study was conducted on 62 adult critically ill patients with sepsis and its related syndromes who were admitted to Ain Shams Uni-versity hospital general intensive Critical Care Unite, from November 2017 to February 2018. Serum level of presepsin and procalcitonin were measured on admission, 24 and 72 hours after admission. Results: There was positive significant correlation between procalcitonin and APACHE II score started from day 0 with p-value 0.011 and started to show strong direct correlation till day 3. Also, there was positive linear significant correlation between procalcitonin and values of SOFA score started from day 1 with p-value 0.005 and started to show strong direct correlation till day 3 with p-value 0.0001. While, there was significant correlation between presepsin and value of APACHE II score at day 0 with p-value 0.006 then insignificant correlation at day1 and started to show strong direct correlation at 3rd day with p-value 0.0001. Also, there was positive linear significant correlation between presepsin and values of SOFA score started from day 0 with p-value 0.035 and started to show strong direct correlation till day 3 with p-value 0.0001. Conclusion: Presepsin cannot differentiate between sepsis and non-infective SIRS since admission; it can predict severity, prognosis and patient outcome. The accuracy of presepsin in this context was seen by our results to be superior to PCT.