Background/Aims: Polymyxin B-immobilized fiber (PMX-F) treatment is reported to be safe and effective in patients with severe sepsis and septic shock. The aim of the present study was to determine whether plasma levels of interleukin (IL)-18, which is linked with sepsis, are associated with plasma endotoxin levels and sepsis-related scores and whether PMX-F treatment affects these variables in patients with septic shock. Patients and Methods: Twenty-six patients with septic shock (15 men and 11 women; mean age 56.5 years) and 20 age-matched healthy subjects (12 men and 8 women; mean age 54.0 years) were included in this study. Septic shock patients were divided into 2 groups: a PMX-F treatment group (9 men and 5 women; mean age 57.5 years) and a conventional treatment group (7 men and 5 women; mean age 55.3 years). Standard supportive care was continued without change during PMX-F treatment. Plasma endotoxin, plasma IL-18, and clinical variables were measured before, immediately after the first and second PMX-F treatment, and the following day. Results: The plasma IL-18 levels were significantly higher in septic shock patients (1,320 ± 360 pg/ml) than in healthy volunteers (140 ± 60 pg/ml; p < 0.001). The IL-18 level was significantly correlated with the plasma endotoxin level (p < 0.001), the Acute Physiology and Chronic Health Evaluation II score (p < 0.01), the Sepsis Severity Score (p < 0.01), the number of failed organs (p < 0.01), and the Goris score (p < 0.01). PMX-F treatment reduced the plasma endotoxin and IL-18 levels significantly after the first treatment (p < 0.05), after the second treatment (p < 0.01), and on the following day (p < 0.001). However, these variables did not change significantly during conventional treatment. Conclusions: IL-18 may be associated with the severity of septic shock, and PMX-F treatment is effective in reducing the IL-18 level in patients with septic shock.