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In this study there were investigated the changes in surface marker CD44 in human erythrocytes exposed to cryoprotective media, as well as the impact of oxidative modification of membrane-cytoskeleton proteins on the CD44 characteristics under the changed physico-chemical parameters of the cellular environment. Glycerol, DMSO, sucrose, and PEG-1500 were shown to cause a decrease in CD44 expression level and amount of CD44-positive cells during prolonged exposure erythrocytes with them. That may reflect subtle adjustments in the system of protein-protein interactions in erythrocyte membrane-cytoskeleton complex, which may affect the stability of cells during cryopreservation. Extracellular substances (sucrose and PEG-1500) exhibited a more pronounced effect on the CD44 in erythrocytes in comparison with the examined substances of endocellular type. Modification of membrane-cytoskeleton proteins with oxidizing bifunctional reagent diamide enhanced the identified tendencies.