Improved markers of resuscitation are needed in patients with severe burn injuries. In previous animal and human work, we showed 1) wound hypoperfusion plays a role in burn depth progression, 2) that there are periods of repetitive ischemia and reperfusion which correlate closely to wound hypoperfusion, and 3) that wound and splanchnic bed CO2 measurements are dependent on the adequacy of resuscitation. We and others believe that current markers for resuscitation, urine output (U/O), and mean arterial pressure (MAP), lag behind in reflecting wound perfusion. In this study, we explore whether gastric and tissue tonometry are better in reflecting minute-to-minute changes in wound perfusion in humans. During the 48-hour experimental period, burn wound, gastric, and arterial pH, Pco2, and PaO2 were measured every 6 seconds using a Paratrend 7 monitor in four patients with life threatening burns. Slopes of change were analyzed and a proportion derived relative to pooled data on 5-minute intervals. Serum lactate, U/O, and MAP were recorded. Laser Doppler Imager (LDI) scans were performed on burn areas every 4 hours, allowing real-time determination of burn perfusion. Resuscitation followed current clinical guidelines. All four patients eventually succumbed, one doing so during the observation period. In the remaining three, U/O and MAP goals were met within 2 hours of resuscitation. Our analysis shows cyclic changes in burn wound pH, CO2, and PaO2, gastric CO2, and PaO2, and arterial base deficit (all P < .005). LDI showed cyclic changes in perfusion (P < .0001) which closely mimic the changes in wound pH, gastric CO2, and arterial base deficit. These changes preceded changes in U/O, MAP, and lactate. Although U/O, MAP, and serum lactate reflect changes in burn wound perfusion, they lag behind other markers. Tissue pH and CO2 and gastric CO2 seem to be more timely related to changes in actual burn perfusion.