Objectives: To define the hemodynamic and gastric intramucosal Pco(2) (Pco(2)) changes during the first 48 hrs after burn trauma and to analyze their relationship with outcome. Design: Prospective, observational study in a cohort of consecutively admitted critically ill burn patients. Setting: Intensive care burn unit in a university hospital. Patients: Forty-two patients with burns covering >20% of body surface area or inhalation injury. Interventions: None. Measurements and Main Results: Patients were monitored with an oximetric pulmonary arterial catheter and a gastric tonometer to measure Pco(2). The difference between arterial and gastric mucosal Pco(2) (P[i-a]co(2)) was considered indicative of gastric mucosal hypoxia. Hemodynamic and Pco(2) measurements were performed during the first 48 hrs after admission. Patients suffered burns covering 36.1% +/- 14.3% (mean +/- so) and 45.3% +/- 21.9% of body surface area (survivors and nonsurvivors, respectively). All patients were successfully resuscitated by conventional standards. Nonsurvivors (n = 16) died a median of 17 days after admission. In univariate analysis, the presence of shock during the resuscitation phase, age, mixed venous pH, P[i-a]co(2), right atrial pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac index, systemic and pulmonary vascular resistance, left ventricular stroke work index, mixed venous oxygen saturation, and systemic oxygen delivery, consumption, and extraction ratio, measured over the first 12 hrs after admission, were significantly (p < .05) different between survivors and nonsurvivors. These differences disappeared after 12 hrs after admission. Multivariate analysis identified age, percentage body surface area burned, and oxygen delivery index (6 hrs after admission) as factors independently associated with a poor outcome. P[i-a]co(2) (12 hrs after admission) was significantly greater in patients with than in those without inhalation injury (17 +/- 13 torr [2.26 +/- 1.73 kPa] vs. 6 +/- 10 torr [0.79 +/- 1.33 kPa]; p = .005). Patients with a P[i-a]co(2) difference (6 hrs after admission) greater than or equal to 10 torr (1.33 kPa) had a mortality rate of 56% vs. 25% of those patients with <10 torr (p = .044). Conclusions: Our data indicate that there are hemodynamic and biochemical changes that occur early after burn trauma that are associated with prognosis after an apparently successful resuscitation. Particularly, a hemodynamic profile characterized by systemic acidosis, low systemic blood flow, and systemic and pulmonary vasoconstriction early after trauma is associated with a poor outcome. Additionally, intestinal mucosal acidosis occurs after burn trauma, is influenced by inhalation injury, and is a variable related to outcome.