Just as a rise in water temperature reduces the supply of O₂ available to water-breathing animals, an increase in altitude reduces the O₂ supply for air breathers. At all altitudes, O₂ makes up 20.9 percent of the dry air; however, as you go up in altitude, the total amount of gas per unit of volume decreases, as reflected in the atmospheric pressure. For example, at 5,800 meters, atmospheric pressure is only half what it is at sea level, so the P_O2 at that altitude is only about 80 mm Hg. At the summit of Mount Everest (8,850 m), P_O2 is only about 50 mm Hg—roughly one-third what it is at sea level.

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Because the movement of O₂ across respiratory gas exchange surfaces and into the body depends on diffusion, its rate of movement depends on the P_O2 difference between the air and the body fluids. Therefore the drastically reduced P_O2 in the air at high altitudes constrains O₂ uptake. Because of this, mountain climbers attempting peaks such as Mount Everest or K2 usually breathe O₂ from pressurized bottles.