Risk of wound infection is increased in morbidly obese surgical patients, in part because a major determinant of wound infection risk, tissue oxygenation, is marginal. Unlike in lean patients, supplemental inspired oxygen (Fio2) only slightly improves tissue oxygenation in obese patients. Mild hypercapnia improves tissue oxygenation in lean patients but has not been evaluated in obese patients. We thus tested the hypothesis that mild hypercapnia markedly improves tissue oxygenation in morbidly obese patients given Fio2 80% during major abdominal surgery. Thirty obese patients (body mass index 61.5 +/- 17 kg/m2) scheduled for open gastric bypass were randomly assigned to normocapnia (n = 15, end-tidal Pco2 35 mm Hg) or hypercapnia (n = 15, end-tidal Pco2 50 mm Hg); Fio2 was 80%. Anesthetic management and other confounding factors were controlled. Tissue oxygen tension was measured subcutaneously at the upper arm using a polarographic probe in a silastic tonometer. Demographic characteristics, cardiovascular measurements, and Pao2 (222 +/- 48 versus 230 +/- 68 mm Hg in normocapnic versus hypercapnic; mean +/- sd; P = 0.705) were comparable in the groups. Tissue oxygen tension, however, was greater in hypercapnic than in normocapnic patients (78 +/- 31 versus 56 +/- 13 mm Hg; P = 0.029). Mild hypercapnia increased tissue oxygenation by an amount believed to be clinically important and could potentially reduce the risk of surgical wound infection in morbidly obese patients.