Background: We studied whether hemodynamic and oxygenation profiles are altered in critically ill patients after exposure to hyperbaric oxygen (HBO). Methods: Ten intensive-care patients (two females, eight males) undergoing HBO treatment after major abdominal surgery, after burn injury and after CO poisoning were included. All subjects were put on mechanical ventilation and received continuous sedation, and had HBO treatment at 2.2 absolute atmospheres for 50 min. Design: Observational prospective study, and repeated measure design. Results: Hemodynamic and oxygen transport patterns were determined before (C0), 1 h (C1) and 2 h (C2) after HBO therapy with continuous cardiac output dual oximetry pulmonary arterial catheter, a central venous and radial arterial line. Data were analyzed with non-parametric repeated measure analysis. Key results are expressed as a percentage of baseline (C0 values correspond to 100%) at C1 and C2 (median values, lower and upper limit of confidence interval): cardiac index [C1: 105% (98–135), C2: 99% (91–117), P = 0.19], systemic (P = 0.62) and pulmonary vascular (P = 0.76) resistance indices were unchanged, but pulmonary venous admixture (Qs/Qt) increased [C1: 173% (112–298), C2: 140% (92–241), P = 0.00002)] and arterial oxygen tension decreased [C1: 76% (67–94), C2: 82% (72–112), P = 0.010]. Conclusion: The hemodynamic profile remained unaffected. The increase in Qs/Qt and the decrease in PaO2 may be attributed to the inhalation of HBO, and both are reversible.