Temperature-sensitive oxygen carriers that are responsive to changes in temperature while maintaining colloidal stability would benefit physiological conditions characterized by tissue hypoxia due to decreased body temperature. These conditions are often accompanied with reduced blood flow and vasoconstriction. Temperature-sensitive oxygen carriers should ideally possess increased oxygen affinity when the body temperature is reduced, to selectively target tissues that are hypoxic as a result of temperature drops. This study expands on previous work, which introduced hydrogel based oxygen carriers as a new class of oxygen carrier that can be synthesized within liposomal reactors via photoinitiated free radical polymerization [Patton, J. N.; Palmer, A. F. Biomacromolecules 2005, 6, 414-24]. In addition to the ability of poly(N-isopropylacrylarnide) hydrogel nanoparticles encapsulating bovine hemoglobin to swell and shrink in response to physiological changes in temperature, the effect of temperature changes on zeta potential, oxygen affinity, and cooperativity are also examined. The methemoglobin level and hemoglobin encapsulation efficiency of hydrogel-based oxygen carriers are also presented. It was observed that nanoscale hydrogel particles swelled as the temperature decreased from 40 to 29 degrees C, which suggests expansion of the hydrogel matrix and reduced resistance to oxygen transport.