Aims: The present study assessed whether plasma levels of thrombomodulin and von Willebrand factor (vWF) are altered in patients with septic shock and whether treatment with polymyxin B-immobilized fiber (PMX-F) affects these levels. Methods: Twenty-four patients with septic shock and 20 normal healthy controls were included in this study. Plasma levels of thrombomodulin and vWF were measured by enzyme immunoassay (EIA). The treatments with direct hemoperfusion using PMX-F column on patients with septic shock were repeated twice for 2 h each. Healthy controls were not subjected to hemoperfusion. Results: 13 of 24 patients with septic shock survived (survival rate was 54.2%). Levels of blood endotoxin decreased significantly from 41.2 ± 4.8 pg/ml at baseline to 13.2 ± 3.6 pg/ml after direct hemoperfusion. Systolic blood pressure increased significantly from 82 ± 6 mm Hg at baseline to 118 ± 12 mm Hg after treatment. The patients with septic shock demonstrated significantly increased plasma levels of thrombomodulin (p < 0.001) and vWF (p < 0.001) compared with those in healthy controls. These increased levels of plasma thrombomodulin and vWF in patients with septic shock decreased significantly after treatment with PMX-F (p < 0.01). Conclusion: These data suggest that plasma thrombomodulin and vWF may be related to septic shock and that PMX-F is effective in reducing these factors in patients with septic shock.