Sepsis is a major public healthcare problem. It remains a significant cause of morbidity and mortality in intensive care units (ICU) all over the world. A lifesaving early specific diagnosis and treatment is a challenge as no gold standard technique exists that can alone allow a rapid and reliable diagnosis of sepsis. Histidine-rich glycoprotein (HRG) is a promising new biomarker of sepsis that can contribute to enhance current sepsis diagnostic tools. The current study aimed to evaluate HRG as a diagnostic biomarker for sepsis compared to the conventionally used biomarkers, procalcitonin (PCT) and Creactive protein (CRP). The study included 67 participants classified into 3 groups: Control (n=19), systemic inflammatory response syndrome (SIRS) patients (n=24) and sepsis patients (n=24). Serum HRG, CRP and PCT levels were measured by ELISA techniques. HRG level was significantly reduced in sepsis patients compared with SIRS patients (P