Background: One of the main components involving in the pathogenesis and prognosis of sepsis and septic shock is natriuretic peptide. Hemodynamic changes in sepsis or septic shock might explain increased plasma levels of these peptides circulations. Objectives: The present study aimed to assess the value of brain natriuretic peptide (BNP) in prediction of sepsis state and its related morbidity. We also attempted to determine the best cutoff point of BNP for diagnosis of sepsis state in those with critical illnesses, admitted to the hospital.Patients and Methods: In a cross-sectional study on critically ill patients referred to infections unit of Hazrat Rasoul Akram Hospital, the enrolled patients were assigned to one of the sepsis (n=30) and nonsepsis (n=30) groups, based on their results of blood culture and clinical manifestations. Plasma level of BNP was measured by immunoassay.Results: In-hospital mortality was only observed in one patient suffering from sepsis. Hospital length of stay (LOS) was significantly longer in the sepsis group compared with the nonsepsis one (17.47±10.10 days versus 7.93±2.92 days). The plasma BNP level, as a marker, was significantly higher in the sepsis group than the nonsepsis one (786.87±164.11 ng/mL versus 154.57±44.67 ng/mL, P=0.039). The BNP level was significantly correlated with some baseline variables including respiratory rate (beta=0.295, P=0.022) and ESR measurement (beta=0.296, P=0.022), but not with other characteristics. Through multivariable linear regression analysis, having other patients' variables information including demographics and hemodynamic parameters, the BNP level was significantly higher in the sepsis group compared with the nonsepsis one (odds ratio=1.008, P=0.046). According to the receiver operating characteristic (ROC) curve analysis, BNP measurement had an acceptable value for discriminating sepsis and nonsepsis states (c=0.734, 95% CI: 0.605-0.864, P=0.002). The optimal cutoff point of BNP for discriminating sepsis and nonsepsis states was 170 ng/mL, yielding a sensitivity of 66.7% and a specificity of 60.0%. Conclusions: Elevated BNP level was associated with a significantly increased risk of sepsis state in critically ill patients.