OBJECTIVE Standard resuscitation practice for shock states mandates use of high flow, high concentration oxygen. However, this may induce microvascular constriction and potentially impair regional oxygen delivery. We thus investigated the impact of varying inspired oxygen concentrations in a rat model of progressive haemorrhage. METHODS Tissue oxygen tension (the balance between local O2 supply and demand) was measured in four different organ beds (liver, renal cortex, muscle, bladder), with concurrent assessment of cardiorespiratory function and organ perfusion in a spontaneously breathing, anaesthetised rat model. 10% aliquots of circulating blood volume were removed at 15 min intervals until death. Different oxygen fractions in the gas mixture (0.15-1.0) were administered following 20% blood removal. A control group consisted of normovolaemic animals breathing varying oxygen fractions. RESULTS Survival times following progressive haemorrhage were similar in animals breathing room air (98 +/- 10 min), 60% O2 (102 +/- 6 min) or 100% O2 (90 +/- 4 min), but significantly worse in those breathing 15% O2 (52 +/- 8 min, P < 0.01). Significant derangements of blood pressure, aortic blood flow and lactataemia were observed in both hypoxaemic and hyperoxaemic groups compared to normoxaemic animals. Breathing 100% O2 increased arterial PO2 sevenfold and tPO2 approximately threefold over baseline values during normovolaemia and mild haemorrhage (20% blood volume removal). However, with progressive haemorrhage, and despite maintained PaO2 values, tissue PO2 fell in line with the decrease in global oxygen delivery. CONCLUSIONS Hypoxaemia and hyperoxaemia both compromised haemodynamics and biochemical markers of organ perfusion during severe, progressive haemorrhage. This may carry implications for resuscitation practice.