Raftlin is a major protein in lipid raft. The aim of this study was to evaluate blood levels of raftlin in septic patients. A prospective study of 82 patients with sepsis was conducted. Human umbilical vein endothelial cells (HUVECs) or mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice) or subjected to cecal ligation and puncture (CLP) surgery. Data showed that LPS induced upregulation of the synthesis and secretion of raftlin in LPS-treated HUVECs, and LPS-injected and CLP-mice. In patients admitted to the intensive care unit with sepsis, circulating levels of raftlin were significantly elevated, compared with control donors. Raftlin levels were higher in patients with septic shock, 891.6 (789.7-1,087.8, n = 30) than in patients with severe sepsis, 681.6 (480.1-819.6, n = 22) or sepsis, 496.1 (418.1-738.9, n = 30), compared with healthy volunteers 364.9 (312.1-392.4, n = 21). These results suggest that in septic patients, raftlin blood level is related to the severity of sepsis and the outcome of the patient and may represent a novel marker of endothelial cell dysfunction, and that raftlin can be used as a biomarker for determining the severity of sepsis.