We investigated whether direct hemoperfusion with a polymyxin B column (DHP-PMX) was able to decrease macrophage and monocyte activity in patients with sepsis. Nineteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome (SIRS) due to infection and a mean arterial blood pressure ≥65 mm 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. Serum neopterin was measured four times: before DHP-PMX, and 24, 48, 72 h after it had begun. The serum concentrations of neopterin were 654 ± 234 nmol/L prior to DHP-PMX vs. 573 ± 196 nmol/L at 24 h, 452 ± 161 nmol/L at 48 h, and 372 ± 139 nmol/L at 72 h, showing a significant decrease from 48 h onwards compared with before treatment. These data suggest that DHP-PMX decreases macrophage and monocyte activity.