To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested whether the five proteins were predictors of clinical severity, which was evaluated by simplified acute physiological score (SAPS), number of organ failures (MOF), acute lung injury (ALI), and subsequent final outcome. Levels of the five plasma markers were higher in patients with severe infection (n = 25) than in patients without sepsis (n = 7) and healthy volunteers (n = 9). In the study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for nonsurvivors as well as for patients with septic shock or with bacteremia, and they were correlated with SAPS and MOF. Survival outcome was predicted with high sensitivity and specificity by initial plasma levels of sICAM-1 and vWf:Ag. The initial sICAM-1 level appeared to be an independent prognostic variable, based on a logistic regression analysis. Unlike sE-selectin, sICAM-1 remained at high levels indefinitely in nonsurvivors. We conclude that, unlike neutrophil activation markers, levels of endothelium-derived soluble adhesion molecules and vWf:Ag in severe sepsis syndrome are correlated with the severity of illness and may be considered as predictors of survival outcome.