The oxygen carried inside plasma performs differently than the oxygen carried inside red cells. Only 0.13-0.3 mL of oxygen in 100 mL of blood is available inside plasma while 14-19 mL of oxygen is carried inside red cells. Thus, less than 5-8 mL of oxygen is available in the plasma of the entire body. When a patient develops hypovolemic shock, red cells are bypassed and are not perfused directly inside the tissues. However, plasma should reach such hypoxic tissues. Thus, an infusion of oxygen-carrying macromolecules in plasma with a hemoglobin concentration of only 6% and P50 value of 24 mm Hg should be therapeutically effective even if less than 100 mL of stabilized hemoglobin solution (conjugated hemoglobin of 90,000 Da with a molecular size of less than 10 nm or 0.01 microm) are infused under shock conditions. The basic physiology of oxygen-carrying macromolecules is described in detail, which is different from the oxygen carried inside the red cells and inside encapsulated oxygen-carrying particles (typically 250 nm or 0.25 microm). Thus, the oxygen-carrying macromolecues are extremely effective in the treatment of shock patients. In emergency cases, after the bleeding is controlled, a small infusion volume of oxygen-carrying macromolecules will supply sufficient oxygen to the hypoxic tissues and immediately improve the blood pressure of shock patients.