AbstractSystemic bacterial infection carries a high risk of mortality in critical care patients. Improvements in diagnostic procedures are required for effective management of sepsis. Recently, the soluble CD14 subtype, or presepsin, has been suggested as a reliable marker of sepsis, and we set out to compare its diagnostic performance with that of procalcitonin (PCT). We focused on a cohort of septic patients who, during their hospitalization, relapsed after a period of clinical relief from symptoms.In total 21 adult patients were studied during their hospitalization in the Critical Care Unit of Policlinico Umberto I hospital; 74 plasma samples were collected at multiple time points, and presepsin levels were measured using a PATHFASTPresepsin and PCT were significantly lower in healthy controls than in sepsis or severe sepsis (p<0.001), both enabled a significant difference to be detected between systemic inflammatory response syndrome (SIRS) and severe sepsis (p<0.05). The area under the curve (AUC) calculated from the receiver operating characteristic (ROC) curve analysis was 0.888 for presepsin and 0.910 for PCT. In those patients in whom a clinical recurrence of sepsis was observed, while PCT levels normalized during the transient remission phase, presepsin levels (>1000 pg/mL) remained high.This study confirms the importance of monitoring a combination of several biomarkers in order to obtain a reliable diagnosis. Maximal presepsin levels could alert clinicians not to suspend antibiotic treatments and to carefully monitor septic patients’ state of health, even after clinical symptoms have disappeared and PCT levels returned to normal.