The delivery of oxygen to tissue by cell-free carriers eliminates intraluminal barriers associated with red blood cells. This is important in arterioles, since arteriolar tone controls capillary perfusion. We describe a mathematical model for O 2 transport by hemoglobin solutions and red blood cells flowing through arteriolar-sized tubes to optimize values of p50, Hill number, hemoglobin molecular diffusivity and concentration. Oxygen release is evaluated by including an extra-luminal resistance term to reflect tissue oxygen consumption. For low consumption (i.e., high resistance to O 2 release) a hemoglobin solution with p50=15 mmHg, Hill n=1, D HBO2 =3×10 −7 cm 2 /s delivers O 2 at a rate similar to that of red blood cells. For high consumption, the p50 must be decreased to 5 mmHg. The model predicts that regardless of size, hemoglobin solutions with higher p50 will present excess O 2 to arteriolar walls. Oversupply of O 2 to arteriolar walls may cause constriction and paradoxically reduced capillary perfusion.