Physiologic changes at high altitude enhance oxygen delivery to tissues through respiratory, hematological, and cardiovascular adaptations. High altitude exposure increases the risk for acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema. In mammals and other air-breathing vertebrates that live at high altitude, adjustments in convective O 2 transport via changes in blood hemoglobin (Hb) content and/or Hb-O 2 affinity can potentially mitigate the effects of arterial hypoxemia. Oxygen uptake at extreme altitudes is markedly limited by the diffusion properties of the blood gas barrier. As a consequence the maximal oxygen consumption of a climber near the summit of Mount Everest is near his basal oxygen requirements. It discusses the physiological and biochemical strategies employed by these animals to enhance O 2 uptake and delivery, as well as to increase the efficiency of O 2 utilization. Through intensive research, it has been found that the animals and birds that inhabit the higher altitude or shortly known as hypoxia environment have much more O2 hemoglobin affinity, and. At high altitude, the cascade starts at a lower partial pressure of oxygen and there is less oxygen available at each stage of the cascade. People must make biological adjustments to ensure that enough oxygen reaches the cells and the mitochondria, despite the shortage. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin‐oxygen affinity on V̇ O 2 max as a function of altitude. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin-oxygen affinity on V̇ O 2 max as a function of altitude. High-altitude life poses physiological challenges to all animals due to decreased environmental oxygen (O 2) availability (hypoxia) and cold. Supporting high metabolic rates and body temperatures with limited O 2 is challenging. Many birds, however, thrive at high altitudes. From high-altitude species battling hypoxia to deep-diving marine mammals, organisms have evolved unique strategies to overcome oxygen challenges. These adaptations involve changes in respiratory pigments, metabolic rates, and specialized organs.