In lowlanders, high altitude (HA) acclimatization induces hemoconcentration by reducing plasma volume (PV) and increasing total hemoglobin mass (Hbmass). Conversely, Tibetan highlanders living at HA are reported to have a similar hemoglobin concentration ([Hb]) as lowlanders near sea level and we investigated whether this reflects alterations in the PV or the Hbmass response to HA. Baseline assessment of PV and Hbmass was performed by carbon monoxide rebreathing at low altitude (~1,400 m) in Sherpas (an ethnic group of Tibetans living in Nepal) and native lowlanders. Participants then ascended to the Everest Base Camp (5,400 m), where further measurements were performed after ~2 days (EBC 1) and ~6 weeks (EBC 2). While on EBC 1 an increase in [Hb] was observed in lowlanders (p=0.004), but not in Sherpas (p=0.179), marked increases in [Hb] were observed in both groups on EBC 2 (p<0.001). On EBC 1, Hbmass (Sherpas, p=0.393; lowlanders, p=0.123) and PV (Sherpas, p=0.348; lowlanders, p=0.172) were not different from baseline in either group, whilst circulating erythropoietin was increased in both groups (p<0.001). On EBC 2, large increases in Hbmass and reductions in PV were observed along with elevated circulating erythropoietin in both groups (all p<0.002). Neither the increases in erythropoietin on EBC 1 (p=0.846) or EBC 2 (p=0.564), nor the expansion of Hbmass (p=0.771) or reduction in PV (p=0.099) on EBC 2 differed between the groups. We conclude that the hematological response of Sherpas to extended exposure to very high altitude does not fundamentally differ from that of native lowlanders.