Blood heparin-binding protein (HBP) for diagnosing bacteremia in patients with sepsis has not been fully investigated. This study aims to explore the diagnostic value of blood HBP in predicting bacteremia in patients with sepsis compared with procalcitonin (PCT), Interleukin 6 (IL-6), C-reactive protein (CRP), white blood count (WBC), and neutrophil. In this observational study, we enrolled consecutive 146 patients, who were divided into two groups as the bacteremia group (n = 57) and the control group (n = 89). HBP, PCT, IL-6, CRP, WBC, and neutrophil were measured. The Chi-squared test and Student's t-test were used to compare the baseline characteristics. The area under the receiver operating characteristic curve (AUC) was calculated to describe the diagnostic accuracy of the biomarkers for predicting bacteremia in patients with sepsis. Spearman's correlation was used to analyze associations between the biomarkers. The concentration of HBP (204.13 ± 87.30 ng/mL ) in the bacteremia group was significantly higher than that in the control group (81.43 ± 61.53). HBP achieved the largest AUC for predicting bacteremia, with a value of 0.88 (95% confidence interval [CI], 0.82-0.94 ). This value was higher than those of the other biomarkers: 0.78 (95% CI 0.69-0.86) for PCT, 0.59 (95% CI 0.48-0.70) for IL-6, 0.56 (95% CI 0.45-0.67) for WBC, 0.73 (95% CI 0.64-0.83) for CRP, and 0.64 (95% CI 0.53-0.74) for neutrophil. The best cut-off value of blood HBP for identifying bacteremia was 95.69 ng/mL, with a sensitivity of 88.64%, a specificity of 68.06%, a positive predictive value of 64.1%, and a negative predictive value of 89.71%. A significant association was found between HBP and CRP (Spearman's rho = 0.528, p <
0.01). However, the correlations among PCT, IL-6, WBC, and neutrophil (Spearman's rho <
0.5, p <
0.01) were relatively weak. Blood HBP may be a useful auxiliary diagnostic marker that is preferable over PCT, IL-6, CRP, WBC, and neutrophil in identifying bacteremia in patients with sepsis.