Objective This study was performed to evaluate the diagnostic value of the neutrophil CD64 index in patients with sepsis in the intensive care unit (ICU). Methods Patients with sepsis who were treated at the ICU of the authors’ institution from December 2016 to June 2018 were retrospectively reviewed. The controls comprised age- and sex-matched patients who underwent coronary bypass and had no evidence of infection. The neutrophil CD64 index, C-reactive protein (CRP) level, and procalcitonin level were compared between the two groups. The diagnostic performance of these measures, including the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve, was examined. Results In total, 35 patients with sepsis and 27 control patients were included in the data analysis. The sensitivity of the neutrophil CD64 index, CRP level, and procalcitonin level was 83%, 74%, and 77%, respectively. The specificity was 88%, 86%, and 81%, respectively. The area under the ROC curve was 0.923 [95% confidence interval (CI), 0.856–0.989], 0.904 (95% CI, 0.832–0.976), and 0.863 (95% CI, 0.776–0.950), respectively. Conclusion The neutrophil CD64 index is a valuable biomarker for diagnosing sepsis in patients in the ICU.