CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.