nd: Sepsis is a global, life-threatening health priority. Blood culture is the gold standard of diagnosis of sepsis, however, it requires several days, which delays the diagnosis of the sepsis. Biomarkers could play a pivotal role in diagnosis, grading and predicting the outcome of sepsis. Objectives: To assess the potential role of C-reactive protein (CRP), procalcitonin (PCT) and presepsin for diagnosis, grading and predicting the prognosis of sepsis. Methods: The study included 28 patients diagnosed with sepsis, and 28 intensive care unit (ICU) patients presented by different presentations but with no sepsis. For patients with sepsis, APACHE II score was calculated, blood culture was done using BacT/Alert system, and Vitek 2 to identify bacterial isolates. For all subjects included in the study, quantitative measurement of CRP, PCT and presepsin were done using PA54 Specific Protein Analyzer, VIDAS® immune-analyzer, and PATHFAST fully automated immunoassay analyzer, respectively. Results: APACHE II score positively correlated with PCT (p=0.026) and presepsin (p=0.034), but not CRP (p=0.291). Differences between cases and control group for the three biomarkers’ levels were statistically significant (P value <0.001). For sepsis severity, there were significant increase in PCT and presepsin on admission (P value <0.001) among septic shock compared to sepsis cases. Procalcitonin was slightly superior than presepsin. Procalcitonin and presepsin showed statistically significant increase (P <0.001 & p=0.02 respectively) among died compared to survived subgroups. Conclusion: PCT and presepsin are reliable biomarkers for early diagnosis, grading and predicting of the prognosis of se