Cardiopulmonary bypass (CPB) is associated with an immunological injury that may cause pathophysiological alterations in the form of a systemic inflammatory response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS). Previous studies on this issue have reported different changes of immunological parameters during and after CPB, but there are no reports about the lipopolysaccharide-binding protein (LBP) in relationship to other markers of inflammation in patients with MODS following cardiovascular surgery. In the present study, we investigated the acute-phase response of patients with MODS of infectious and non-infectious origin following open-heart-surgery. Plasma levels of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP were measured in the first four postoperative days in 12 adult male patients with the signs of SIRS and two or more organ dysfunctions after myocardial revascularization (MODS-group), and 12 patients without organ insufficiencies (SIRS-group). There were no significant differences regarding age, weight, height, preoperative NYHA-classification, preoperative LVEDP, or the number of anastomosis. Patients with MODS had a significantly longer operation time, duration of ischemia, and duration of extracorporeal circulation. None of the patients in the SIRS group died, whereas in the MODS group, 4 patients died due to septic multiorgan failure. Plasma PCT and IL-6 concentrations were significantly elevated in all MODS patients. CRP and LBP showed no differences between the MODS and the SIRS group. Comparing the MODS patients with and without positive microbial findings, we found significantly elevated levels of PCT and LBP in those patients with documented infections. Our results indicate that LBP may be a new marker for the differentiation between a severe non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative course following CPB, while a microbiological result is still missing.