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Red blood cells (RBCs) play a crucial role in oxygen transport in livingorganisms as the vast majority of oxygen in the blood is bound to thehemoglobin molecules in their cytosol. Healthy RBCs have a biconcave shape anda flexible membrane enabling them to undergo substantial reversible elasticdeformation as they traverse narrow capillaries during microcirculation. ThisRBC deformability is critical for efficient circulation while the uniquebiconcave shape of healthy RBCs is attributed to their specific volume, whichaffects the amount of oxygen they can carry. However, despite extensiveresearch, the underlying mechanism that determines the optimal RBC volumeremains unknown. This paper examines the impact of RBC volume on the efficiencyof oxygen transport from a fluid dynamics standpoint. Our investigation revealsthat RBCs with volumes similar to those observed in vivo demonstrate superioroxygen transport efficiency in circular tubes similar to arterioles, whichrepresent areas of the circulatory system with the highest flow resistance.Furthermore, we identify mechanisms that impair oxygen transport when the RBCvolume deviates from the optimal value. While healthy RBCs produce a maximumcell-free layer thickness that affects flow dissipation, smaller RBC volumesresult in greater deformations and thus dissipate more energy. Strikingly, theflow resistance is minimized at the reduced volume of healthy RBCs. Our studyhighlights that the volume of healthy RBCs maximizes oxygen transportefficiency and may offer insight into developing targeted treatments forcirculatory disorders.

The volume of healthy red blood cells maximizes oxygen transport