Virtually all therapeutic interventions failed to improve sepsis survival. One potential explanation is the heterogeneity of the immune response to sepsis such that only a portion of the patients die due to excessive inflammation. The clinical trials lacked power since traditional measurements do not accurately identify these patients. Previous work has shown that higher plasma levels of IL-6 are found in those mice that die from septic peritonitis, therefore we sought to determine if IL-6 measured 6 hours after surgery would predict outcome. Adult, female BALB\c mice (n=79) were subjected to cecal ligation and puncture (CLP) and treated with imipenem in D5W every 12 hours for 5 days to result in an initial homogenous population. Six hours after surgery, blood from the tail vein was used to measure IL-6 and survival followed for 21 days. Survival at 3 days was 77% and at 21 days 44%. Plasma IL-6 levels >2 ng/ml predicted 3 day mortality (sensitivity: 58%, specificity: 97%). A weighted formula combining body mass, lymphocyte and platelet count obtained 24 hours after CLP also predicted death (sensitivity: 83%, specificity: 79%). Mice who would live beyond the first three days had a significant decrease in body weight compared to survivors. 24 hours after CLP, survivors also had increased circulating neutrophils and decreased lymphocytes. We tested the value of the IL-6 prediction by surgically resecting the cecum in those animals with IL-6 > 2 ng/ml, which resulted in a significant improvement in survival. Newer multiplex technologies have confirmed these results and defined additional cytokine markers which predict sepsis mortality. The multiplex technology defined that both proinflammatory and anti-inflammatory cytokines are elevated during the early phase of sepsis. These data demonstrate that IL- 6 measured 6 hours after injury accurately predicts mortality resulting from experimental sepsis. This measurement may be determined quickly so that therapy may be targeted only to those individuals at significant risk of dying, and started within sufficient time to be effective.