ABSTRACT Background: Sepsis is a potentially fatal illness caused by an unbalanced host response to infection. Sepsis is becoming more common, indicating that it is a main cause of severe disease and fatality globally. Patients with sepsis commonly have simultaneous acute kidney injury (AKI), with rates ranging from 5 to 20% among hospital admissions and increasing to 35-50% among the seriously sick. Because proenkephalin is not bound to proteins in plasma and is only filtrated in the glomerulus, it is a promising biomarker for renal impairment in critically sick patients. Objective: The aim of the current study was to assess Proenkephalin A119-159 (penKid) as a biomarker for sepsis related AKI in ICU patients. Patients and methods: A case control study was conducted at intensive care unit (ICU) department, Benha Faculty of Medicine on a total of 80 subjects which were divided into 50 septic AKI cases and 30 matched age and sex controls. Subjects met two or more SIRS-criteria and their estimated glomerular filtration rate (eGFR) was determined by the formula derived from the Modification of Diet in Renal Disease (MDRD) Study and the Proenkephalin A119-159 (penkid) was measured by ELISA. Results: The current study demonstrated that, septic AKI cases demonstrated significant increase in penkid compared to control group(p