This prospective, non-interventional study was conducted in a medical adult intensive care unit to determine the usefulness of procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determinations in the diagnosis of nosocomial sepsis. Serum PCT and bronchoalveolar lavage fluid sTREM-1 concentrations were measured in 50 critically ill patients suffering from nosocomial sepsis. Ventilator-associated pneumonia (VAP) was diagnosed in 31 patients and extrapulmonary sepsis in 19. Increase serum PCT concentration (>0.15 ng/ml) was found in 44 (88%) patients and was higher in those suffering from a non-pulmonary sepsis. The concomitant BAL sTREM-1 determination correctly classified pulmonary (VAP) versus non-pulmonary origin in 41 out of 44 cases (93%). Even when PCT concentration remained low, sTREM-1 assessment allowed for the detection of the sepsis (VAP) in 50% of cases. Both PCT and sTREM-1 concentrations were low in only 3 patients (6%) in whom sepsis could have been missed if only diagnosed by the measurement of these 2 biomarkers. We therefore concluded that the combined measurement of serum PCT and BAL sTREM-1 concentrations could be of interest in detecting the presence of a nosocomial sepsis and in discriminating VAP versus extrapulmonary infection.