Background: Sepsis in chronic liver disease (CLD) patients with high mortality and morbidity rates. Therefore, early detection in these patients may improve prognosis of the disease. CD14 may be a promising biomarker in the diagnosis of sepsis. Objectives: Our study aimed to evaluate presepsin (sCD14) as an early diagnostic marker in septic patients with CLD. Its value was compared to that of CRP, and total leucocytic count (TLC) for diagnosis of bacterial infection. Methodology: The study included 60 patients with sepsis in addition to 30 healthy subjects as controls. Complete blood count, CRP, liver and renal function tests as well as blood culture were performed. Identification of the isolated organisms and antibiotic susceptibility testing were performed using VITEK2 compact system and sCD14 was measured by ELISA. Results: Levels of sCD14 were significantly higher (P<0.001) in septic patients compared with controls. ROC curve revealed that the sCD14 had a higher diagnostic performance than that of CRP and TLC (P<0.001). The sCD14, at cutoff level greater than 0.89 mg/L, had 91.67% sensitivity and 63.33% specificity. Conclusion: sCD14 is more sensitive and specific for diagnosis of sepsis compared with CRP and TLC.