Résumé : Objectives: Efficient empiric antibiotic therapy remains the cornerstone of sepsis treatment. However, antibiotics could be responsible for the transient clinical deterioration provoked by the release of bacterial cell-wall constituents, such as endotoxin, into the blood stream. The aim of this study was to evaluate if a transient elevation of endotoxin level occurred in septic patients following antibiotic administration. Methods: Thirty-three septic intensive care unit (ICU) patients were enrolled in this prospective trial. Four blood samples were collected from each of these patients during a 24-h period, and endotoxin activity was measured in these samples by the chemiluminescence technique. Fifteen ICU non-septic patients and 15 healthy volunteers were also observed for possible daily fluctuations in endotoxin activity. Results: There was no significant increase in endotoxin levels following the initiation of empiric antibiotic therapy in septic patients. A clinical deterioration in the 4 h following antibiotic administration was observed in 14 septic patients (42 %). These patients had significantly higher endotoxin levels than stable septic patients. Conclusions: Although endotoxin levels failed to increase after the administration of antibiotic(s) to critically ill patients, they were higher in the septic patients presenting a transient deterioration than in the other patients. This observation suggests that a possible release of endotoxin due to bacteria lysis by antibiotics could be responsible for the observed clinical deterioration. © 2014 Springer-Verlag.