Limitations of the studyThis study is observational and somewhat limited because of the nominal number of included patients, although thoroughly matched with regard to timing inclusion and general characteristics of the study population. Although our initial gold standard diagnosis for sepsis was a clinical one with a relatively low likelihood ratio, it was further validated by a microbiological confirmation, but re-allocations were mandatory. Selection of parameters, especially neurocorticotropic markers, while arbitrary, was nonetheless based on recent knowledge relative to coexpression of studied neuropeptides and cytokines (SDF-1��, AVP, copeptin, APL) in the CNS. A not-highly sensitive PCT measurement has been selected. In the multiple regression analysis, the use of more than three variables with a limited sample did not definitely avoid possible overfitting. The alternative diagnostic combination of parameters (cortisol baseline, ACTH) proposed to challenge PCT measurement in early sepsis diagnosis is not necessarily always easier or faster to obtain in all centers. Of course, a larger study should further validate the diagnostic usefulness of this biomarker combination.ConclusionsThe neuro-corticotropic systemic stress response of early admitted ICU patients is differentially profiled with special emphasis on sepsis. An alternative diagnostic combination of categorical parameters (cortisol baseline, ACTH) was as efficient as PCT or sepsis score in identifying critical sepsis, and all together offered the best performance. This might help ICU physicians in refining bedside diagnostic tools, in addition to traditional microbiological sampling and decision-making strategies, and calls for further validation on a larger population.Key messages? The neuro-corticotropic stress response (ACTH/cortisol baseline, copeptin, apelin, SDF-1��) is in someway different in septic vs. non-septic early admitted ICU patients.? Adding cortisol baseline and ACTH to PCT blood measurement or sepsis score -gold standards- in a combination of variable score analyses helps in refining bedside diagnostic tools to efficiently diagnose sepsis.