Introduction: Since sepsis is a major global health problem, a rapid and correct diagnosis and the initiation of therapy are essential to improve the patient consequences. This study aimed to assess the serum levels of calprotectin and a more widely used sepsis biomarker in the patients with bacterial sepsis (BS). Method: Subjects were classified into BS group with the patients who met the sepsis criteria at the beginning of the study and the control group. We investigated the concentrations of biomarkers in 300 blood samples collected at admission from all patients hospitalized in the Fatemeh Al-Zahra Hospital, Najafabad, Isfahan in April 2019 and April 2020. Results: The microbial etiology in the BS group was confirmed in 35 patients (100%). The most frequently cultivated pathogens were Escherichia coli (n=11). The serum concentrations of calprotectin and CRP were significantly higher in the patients with BS (n= 35) than in the healthy controls (n= 20). Conclusion: Our results suggest that the serum level of calprotectin could have the substantial added value to manage BS which is a reliable biomarker of BS.