We prospectively studied (1) the relationships between angiogenic factors, their soluble receptors and organ dysfunction and (2) the effects of disseminated intravascular coagulation (DIC)-induced platelet consumption, thrombin generation, and tissue hypoxia on the expression of the factors and receptors. Fifty patients with sepsis were classified into two subgroups: 37 patients with DIC and 13 patients without DIC. DIC patients showed higher Sequential Organ Failure Assessment (SOFA) scores, the prevalence of multiple organ dysfunction syndrome (MODS) and more increased soluble fibrin and lactate levels. We observed lower levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR2), angiopoietin 1 (Ang1) and Ang1/Ang2, and higher sVEGFR1 and Ang2 levels in DIC patients, but not significant differences in soluble Tie2 expression during the study period. The levels of VEGF, sVEGFR1, and Ang2 in DIC patients correlated with the SOFA scores. Clear differences were observed in the levels of Ang2 in the DIC patients between survivors and nonsurvivors and between those with and without MODS. The area under receiver operating characteristic curves for predicting death and MODS by Ang2 were 0.710 and 0.784, respectively. The VEGF levels showed a marked correlation with the platelet counts. Soluble fibrin and lactate levels independently predicted increases in the levels of VEGF, sVEGFR1, and Ang2 in DIC patients. In conclusion, VEGF, sVEGFR1, Ang2, and Ang1/Ang2, especially Ang2, may have roles in the development of MODS in sepsis associated with DIC, and VEGF, sVEGFR1, and Ang2 serum levels correlated with the extent of DIC-induced platelet consumption, thrombin generation, and blood lactate levels.