Background: Septic encephalopathy is a common term denoting the signs of progressing central nervous system dysfunction in septic patients. Metabolic alterations including amino acid imbalance are involved in the pathogenesis of septic encephalopathy. The aim of the present study was to determine whether the ratio of branched-chain amino acids to aromatic amino acids is altered in patients with septic encephalopathy and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects this balance. Methods: 16 septic patients with encephalopathy, 10 septic patients without encephalopathy, and 20 healthy controls were included in this study. Sepsis was diagnosed according to the ACCP/SCCM Consensus Conference criteria. Plasma endotoxin levels, interleukin-6 (IL-6) levels, and amino acid ratios were measured before and after PMX-F treatment. Results: Within 12 h of the onset of septic encephalopathy, plasma endotoxin and IL-6 levels were increased significantly in septic patients with encephalopathy in comparison to those in septic patients without encephalopathy (endotoxin, p < 0.05; IL-6, p < 0.01) and those in healthy controls (endotoxin; p < 0.001; IL-6, p < 0.001). The ratio of branched-chain amino acids to aromatic amino acids in septic patients with encephalopathy was decreased in comparison to the ratio in septic patients without encephalopathy (p < 0.05) and that in healthy controls (p < 0.01). PMX-F treatment reduced plasma endotoxin (p < 0.01) and IL-6 levels (p < 0.01) and increased the ratio of branched-chain amino acids to aromatic amino acids (p < 0.01). Conclusion: The amino acid imbalance in patients with septic encephalopathy may be a marker for the severity of the septic syndrome, and PMX-F hemoperfusion is effective in ameliorating the increased plasma endotoxin and IL-6 levels and the amino acid imbalance in these patients.