The extinct Steller’s sea cow (Hydrodamalis gigas; †1768) was a whale-sized marine mammal that manifested profound morphological specializations to exploit the harsh coastal climate of the North Pacific. Yet despite first-hand accounts of their biology, little is known regarding the physiological adjustments underlying their evolution to this environment. Here, the adult-expressed hemoglobin (Hb; α2β/δ2) of this sirenian is shown to harbor a fixed amino acid replacement at an otherwise invariant position (β/δ82Lys→Asn) that alters multiple aspects of Hb function. First, our functional characterization of recombinant sirenian Hb proteins demonstrates that the Hb-O2affinity of this sub-Arctic species was less affected by temperature than those of living (sub)tropical sea cows. This phenotype presumably safeguarded O2delivery to cool peripheral tissues and largely arises from a reduced intrinsic temperature sensitivity of theH. gigasprotein. Additional experiments onH. gigasβ/δ82Asn→Lys mutant Hb further reveal this exchange renders Steller’s sea cow Hb unresponsive to the potent intraerythrocytic allosteric effector 2,3-diphosphoglycerate, a radical modification that is the first documented example of this phenotype among mammals. Notably, β/δ82Lys→Asn moreover underlies the secondary evolution of a reduced blood-O2affinity phenotype that would have promoted heightened tissue and maternal/fetal O2delivery. This conclusion is bolstered by analyses of two Steller’s sea cow prenatal Hb proteins (Hb Gower I; ζ2ε2and HbF; α2γ2) that suggest an exclusive embryonic stage expression pattern, and reveal uncommon replacements inH. gigasHbF (γ38Thr→Ile and γ101Glu→Asp) that increased Hb-O2affinity relative to dugong HbF. Finally, the β/δ82Lys→Asn replacement of the adult/fetal protein is shown to increase protein solubility, which may have elevated red blood cell Hb content within both the adult and fetal circulations and contributed to meeting the elevated metabolic (thermoregulatory) requirements and fetal growth rates associated with this species cold adaptation.