ObjectiveTo evaluate the prognostic value of lactate clearance and lactate production in severely ill septic patients with normal or mildly elevated blood lactate concentration.DesignProspective, observational study.SettingNineteen-bed mixed medicosurgical intensive care unit.PatientsFifty-six patients with severe sepsis and blood lactate concentration <3 mmol/L.Measurements and Main ResultsLactate metabolism was evaluated in all patients. Lactate clearance was measured by modeling the change in arterial blood lactate over time induced by an infusion of 1 mmol/kg sodium lactate for 15 mins. Lactate production was calculated as the product of lactate clearance times the blood lactate concentration before the infusion. Outcome was taken to be mortality at 28 days after the beginning of the septic episode. A logistic regression model taking into account different risk factors was constructed. Among the 56 patients, 17 (30.3%) died before the 28th day. Basal blood lactate concentration was not different between survivors and nonsurvivors, whereas lactate clearance and production were higher in survivors (0.86 ± 0.32 vs. 0.58 ± 0.18 L/hr/kg,p< .005, and 1.19 ± 0.63 vs. 0.89 ± 0.24 mmol/hr/kg,p= .055, respectively). An increase in blood lactate 45 mins after the end of the lactate infusion (&Dgr;lact-T60) ≥0.6 mmol/L was predictive of 28-day mortality with 53% sensitivity and 90% specificity. Multivariate analysis showed that only three factors were independently and significantly correlated with 28-day mortality: presence of more than two organ failures (odds ratio, 27;p= .04), age >70 yrs (odds ratio, 5.7;p= .032), and &Dgr;lact-T60 ≥0.6 mmol/L (odds ratio, 14.2;p= .042).ConclusionLow lactate clearance in severely ill septic patients with normal or mildly elevated blood lactate is predictive of poor outcome independently of other known risk factors such as age and number of organ failures.