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Objectives: To determine the oxyhemoglobin dissociation curve in blood with pH of approximately 6.3 due to metabolic and superimposed respiratory acidosis, and to evaluate the oxygen delivery capacity of the blood under these circumstances., Design: In vitro study., Setting: A blood gas laboratory in a university institute for respiratory physiology., Subjects: Heparinized normal human blood., Interventions: The oxyhemoglobin dissociation curve was determined by measuring PO2, pH, PCO2, and hemoglobin oxygen saturation at 37 degrees C in mixtures of blood from two reservoirs, both prepared by titration with lactic acid to a pH of 6.3 during tonometry with gases containing 4.2% CO2 and high and low oxygen percentages, respectively. For determination of the effect of additional increases in PCO2, the reservoir blood thus produced was prepared by further tonometry with gases containing 12.8% CO2 and the same oxygen percentages., Measurements and Main Results: With the same degree of lactic acidosis (blood lactate concentration of 52 mmol/L), the position of the oxyhemoglobin dissociation curve was the same for blood with PCO2 of 30 torr (4 kPa) and pH of 6.295 and for blood with PCO2 of 90 torr (12 kPa) and pH of 6.165. During tonometry with a gas with PCO2 of 30 torr (4 kPa) and PO2 of 20 torr (2.7 kPa) and addition of increasing amounts of lactic acid, leading to a stepwise change in pH from 6.7 to 6.0, hemoglobin oxygen saturation decreased with decreasing pH from 6.7 to 6.4, but remained the same at a pH of between 6.4 and 6.0. The measured rightward shift of the oxyhemoglobin dissociation curve at such a low pH was clearly less pronounced than that calculated using commonly applied equations, in particular, at the lowest pH. The beneficial effects of the rightward shift of the oxyhemoglobin dissociation curve on the estimates of extractable oxygen at a given venous PO2 decrease with decreasing pH, and disappear rapidly when the Pao2 is reduced below normal., Conclusions: The acidemia-induced rightward shift of the oxyhemoglobin dissociation curve does not increase further at a pH < 6.4, and is, at such extreme acidemia, less pronounced than calculated by the commonly used equations. To obtain optimal tissue oxygenation in patients with severe circulatory failure and extreme metabolic acidosis, Pao2 should be > 250 torr (> 33.3 kPa).