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Surface neutrophil CD64 expression is upregulated in patients with bacterial infection. As it was suggested that the CD64 index could be used to detect sepsis in hospitalized patients, we questioned whether the CD64 index could discriminate between septic patients and postoperative surgical patients, defined as systemic inflammatory response syndrome (SIRS), both admitted at the intensive care unit (ICU). Furthermore, we wondered whether the CD64 index was an improved diagnostic compared to standard assays used at the laboratory. For this, outclinic (OC) patients were included as controls.The Leuko64™ assay was used to determine the CD64 index in residual EDTA blood samples from selected septic patients (n=25), SIRS patients (n=19), and OC patients (n=24). Additionally, WBC count, neutrophilic and eosinophilic granulocyte count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured simultaneously.The CD64 index was higher in septic patients compared to both the SIRS and OC group (p<0.0001). In addition, the WBC count, neutrophil count, ESR and CRP were also higher in septic patients than the OC group (p<0.0001). However, only the WBC count, eosinopenia, and ESR were comparable between the SIRS and the sepsis group and proved to be discriminative to the OC group (p<0.05). The CD64 index demonstrated higher sensitivity and specificity than CRP, WBC count, neutrophilic and eosinophilic granulocyte count, and ESR.A high CD64 index was found in septic intensive care patients, while a low CD64 index was observed in OC and SIRS patients, demonstrating that the CD64 index can be used for routine diagnostics in the ICU setting.