Methods for treating blood. The methods comprise obtaining whole blood from a donor, mixing the whole blood with a red blood cell enhancement composition, and incubating the mixture of whole blood and red blood cell enhancement composition. The method can be performed at a time proximate to the time of obtaining blood from the donor, or after the blood has been stored for a period of time. The method rejuvenates red blood cells. Incubation may be performed for a period of time sufficient to increase the level of a metabolically-significant compound in the RBCs in the leukoreduced blood to a level essentially equal to levels found in fresh blood, the level being greater than the level of the compound in non-leukoreduced blood mixed with the RBC enhancement composition and incubated for the period of time.