Compositions and methods for treating red blood cells are disclosed. The methods include contacting a red blood cell sample ex vivo with an amount of nitric oxide or a nitric oxide-releasing compound sufficient to convert at least a portion of the extracellular ferrous hemoglobin present in the red blood cell sample to ferric hemoglobin. Red blood cells administered to a mammal following the ex vivo treatment have reduced adverse effects on the mammal to which they are administered.