Background This study was design to investigate the prognostic value for death at day-28 of lactate course and lactate clearance during the first 24 hours in Intensive Care Unit (ICU), after initial resuscitation. Methods Prospective, observational study in one surgical ICU in a university hospital. Ninety-four patients hospitalized in the ICU for severe sepsis or septic shock were included. In this septic cohort, we measured blood lactate concentration at ICU admission (H0) and at H6, H12, and H24. Lactate clearance was calculated as followed: (lactate initial - lactate delayed )/ lactate initial x 100%. Results The mean time between severe sepsis diagnosis and H0 (ICU admission) was 8.0 ± 4.5 hours. Forty-two (45%) patients died at day 28. Lactate clearance was higher in survivors than in nonsurvivors patients for H0-H6 period (13 ± 38% and −13 ± 7% respectively, p = 0.021) and for the H0-H24 period (42 ± 33% and −17 ± 76% respectively, p < 0.001). The best predictor of death at day 28 was lactate clearance for the H0-H24 period (AUC = 0.791; 95% CI 0.6-0.85). Logistic regression found that H0-H24 lactate clearance was independently correlated to a survival status with a p = 0.047 odds ratio = 0.35 (95% CI 0.01-0.76). Conclusions During the first 24 hr in the ICU, lactate clearance was the best parameter associated with 28-day mortality rate in septic patients. Protocol of lactate clearance-directed therapy should be considered in septic patients, even after the golden hours.