Background: In Japan, the most commonly used hemofilters for patients with acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) are made of polysulfone membranes. The aim of this study was to compare the efficacy of two commercially available polysulfone membranes for the removal of solutes. Methods: This single-institution, prospective cross-over study was conducted between December 2010 and January 2012. Two polysulfone membranes, Hemofeel SHG (Toray) and Excelflo AEF (Asahi Kasei Medical), were compared in eight intensive care unit patients (median age, 80 years; seven men) who had severe sepsis that required CRRT and who required vasopressor treatment to maintain their mean blood pressure above 65 mmHg. The primary outcome measure was the efficacy of solute removal, evaluated for high-mobility group protein 1 (HMGB-1) and myoglobin. Results: The main cause of sepsis was abdominal infection (50%); the mortality was 62.5%. Blood clearance of myoglobin in 1 h was significantly greater with SHG (p = 0.02), particularly at 24 h (p = 0.17). Blood creatinine clearance did not differ significantly between the two membranes after 1 h, but SHG demonstrated slightly greater appearance at 24 h. There were no significant differences between the two membranes in the clearance of other solutes including HMGB-1.Conclusions: This preliminary study compared the use of two polysulfone membranes in patients with sepsis requiring CRRT and showed that the polysulfone membrane SHG was capable of removing myoglobin with greater efficacy.