OBJECTIVE: To evaluate plasma amino acid concentrations and markers of inflammation in the early stage and the course of septic encephalopathy. DESIGN: Prospective, case series of patients with well-defined septic encephalopathy. SETTING: Surgical department and intensive care unit of a university hospital. PATIENTS: Seventeen patients with sepsis according to the ACCP/SCCM consensus conference criteria and encephalopathy based on neuropsychological tests, compared to a control group undergoing uncomplicated thoracic surgery. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: SOFA score, blood samples for plasma amino acids, procalcitonin and interleukin-6. Sepsis was determined to be the cause of encephalopathy in 14 of the 17 patients. Six patients developed septic shock, four died within the study period of 28 days. Within 12 h of the onset of septic encephalopathy, mean values of PCT and IL-6 were elevated ( p<0.001) and the amino acids unbalanced (the ratio of branched-chain to aromatic amino acids was decreased, p<0.001). During the course of sepsis the decreased amino acid ratio was significantly, but moderately, correlated with elevated PCT and IL-6 levels. On study days when PCT was higher than 2 ng/ml, the amino acid ratio was significantly lower. In no patient was severe liver dysfunction seen. CONCLUSIONS: Metabolic disturbances with changes in amino acid levels can occur early in septic patients, without serious liver abnormalities. The present data suggest a possible role of amino acids in the pathogenesis of septic encephalopathy.