The causes of acute hypoxemic respiratory failure are a low inspired concentration of oxygen, alveolar hypoventilation, ventilation-perfusion mismatch, intrapulmonary shunting, a low mixed venous oxygen content, and, rarely, diffusion impairment. Low inspired concentration of oxygen is an uncommon cause of acute hypoxemic respiratory failure. This can occur at high altitudes or when toxic gases are inhaled (e.g., smoke inhalation). Diffusion impairment is a relatively uncommon cause of acute hypoxemic respiratory failure but may occur with severe interstitial lung disease. In patients with acute respiratory distress syndrome, diffusion impairment can contribute to hypoxemia, but shunting is the more important physiologic derangement in this disorder. Pure alveolar hypoventilation is a relatively rare form of acute hypoxemic respiratory failure that is caused by neuromuscular or central nervous system dysfunction (e.g., opiate overdose). Ventilation-perfusion mismatching is the most common pathophysiologic cause of acute hypoxemia. It develops when there is a decrease in ventilation to normally perfused regions of the lung, a decrease in perfusion to normally ventilated regions of the lung, or some combination of a decrease in both ventilation and perfusion. A low mixed venous oxygenation saturation can also contribute to hypoxemia. However, it is uncommon for this to be the only factor contributing to acute hypoxemic respiratory failure.