The fact that thrombomodulin (TM) is released into the bloodstream from damaged vascular endothelial cells led us to hypothesize that plasma levels of soluble TM could be an indicator of the development of organ failure. In this study, we examined the changes in plasma levels of TM in 60 septic patients and 13 postsurgical patients, and investigated the circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) to determine the mechanism causing the excess liberation of TM. The arterial ketone body ratio (AKBR) was also measured as an indicator of the hepatocyte energy state. Of the 60 septic patients, 26 developed organ failure, 10 of whom died. In contrast, none of the postsurgical patients developed organ failure. The mean plasma level of TM was significantly higher in the septic patients who developed organ failure compared to those without organ failure (P<0.001) or the postsurgical patients (P<0.001). Furthermore, those patients whose plasma TM values became elevated over 6.0ng/ml frequently developed complications. A positive correlation was also observed between the plasma TM levels and the IL-6 (P<0.01) and PMNE levels (P<0.01). In contrast, a negative correlation was seen between the plasma TM levels and the AKBR (P<0.01). These findings show that plasma TM could be a useful indicator of impending organ failure during sepsis.