BACKGROUND The treatment of burn patients who undergo mechanical ventilation is complicated by many factors; patient outcomes and mortality could potentially be improved with predictive biomarkers. Severe burn provokes a systemic inflammatory response characterized by the release of a host of cytokines. Recent studies evaluated the prognostic value of temporal changes in cytokine levels in several patient populations, but few have compared differences in the cytokine profiles of survivors and nonsurvivors following severe burn. We previously compared high-frequency percussive ventilation and low-tidal-volume ventilation and found no difference in mortality or cytokine levels between the two treatments. Since it is unknown whether cytokine levels are predictive of mortality in these patients, we performed a post hoc analysis comparing cytokine levels in survivors and nonsurvivors. METHODS We evaluated plasma levels of several cytokines (interleukin 1β [IL-1β], IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α) for their prognostic biomarker potential related to mortality at 0, 3, and 7 days in survivors and nonsurvivors of burns. RESULTS While the majority of values for IL-1β, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α fell below the limit of quantification, univariate analysis demonstrated higher plasma levels of IL-6 and IL-8 in nonsurvivors on Day 7. Logistic regression revealed that elevated plasma IL-8 was independently associated with an increased likelihood of the composite end point of death or ventilator-associated pneumonia with odds ratios of 7.9, 26, and 7.3 on Days 0, 3, and 7, respectively. CONCLUSION Early increases in plasma IL-8 are associated with a multifold increase in death or ventilator-associated pneumonia in mechanically ventilated burn patients.