Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor. The development of capillary leak is common in septic patients, and several sepsis-associated mediators may induce VEGF production. The potential role of VEGF during sepsis has not been studied to date. The aim of the study was first to assess whether circulating VEGF levels increase during sepsis, and second, to examine whether plasma VEGF levels are associated with disease severity. VEGF levels were measured in serial plasma samples of 18 patients with severe sepsis and in 40 healthy controls. VEGF levels were correlated to clinical signs and symptoms. VEGF levels were significantly elevated in sepsis patients compared with healthy controls (134 vs. 55 pg/mL; P <0.001). Serum albumin levels used as an indirect measure of vascular leak were decreased in septic patients. Increased plasma VEGF levels at study entry were correlated to severity of multiple organ dysfunction during the course of disease (Pearson correlation coefficient r=0.75; P=0.001). Moreover, maximum VEGF levels in nonsurvivors were significantly higher than those in survivors (P=0.018). These data show that plasma VEGF levels are elevated during severe sepsis. Furthermore, our data indicate that plasma VEGF levels are associated with disease severity and mortality. Further study of the potential role of VEGF in the development of sepsis-associated capillary leak is indicated.