BACKGROUND & AIMS: Liver organ dysfunction is an important determinant for clinical deterioration and outcome in patients with sepsis. Although glutamate plays a central role in the metabolism of the liver, liver cellular injury during sepsis is clinically determined by plasma values of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The aim of this study was to determine the predictive value of measuring the amino acids glutamate and glutamine concentrations in the early phases of septic shock. METHODS: In a prospective observational study the amino acids glutamate and glutamine were compared to the standard parameters of liver dysfunction used as predictors of outcome in patients with acute liver dysfunction as part of the development of multiple organ failure. RESULTS: Glutamate concentrations were consistently and significantly lower in non-survivors (p=0.03) compared to surviving septic patients. Plasma Glu/Gln ratio was consistently lower in non-survivors compared to survivors (p=0.002). Both parameters were good predictors of outcome (area under the ROC curve) 0.75 (95% CI 0.65-0.85) and 0.82 (95% CI 0.74-0.91) respectively, p<0.0001. Glutamate concentration was an independent and better risk factor for mortality compared to the liver enzyme plasma values. CONCLUSIONS: Patients who die of septic shock with acute liver dysfunction can be predicted by significantly lowered plasma glutamate concentrations and lowered glutamate/glutamine ratios already in the first 24 h of septic shock.