We investigated whether hemoperfusion with a polymyxin B column (DHP-PMX) was able to improve coagulation abnormalities in patients with sepsis. Sixteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome due to infection and a mean arterial blood pressure ≥65mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for intravenous infusion, and DHP-PMX was performed twice within 24 h for 3 h each time. Circulating levels of thrombin–antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), the TAT/PIC ratio, and plasminogen activator inhibitor-1 (PAI-1) were measured six times. Before DHP-PMX, the TAT level was 24.5 ± 8.3 ng/mL, the PIC level was 2.5 ± 1.1 µg/mL, the TAT/PIC ratio was 13.9 ± 3.5, and the PAI-1 level was 143.0 ± 24.4 ng/L. The TAT level, TAT/PIC ratio, and PAI-1 were all significantly lower (P < 0.05) after 48 hr compared with before DHP-PMX, but no significant change of PIC was observed. In these patients with sepsis, fibrinolysis was inhibited by PAI-1, whereas clotting activity was significantly increased. This coagulation/fibrinolysis imbalance was improved by DHP-PMX. The present results suggest that indirect inhibition of clotting activity can be achieved in patients with sepsis through adsorption of lipopolysaccharide by DHP-PMX.