Aim: The hemoglobin (Hb) variants can alter the structure and biochemical functions of Hb along with affecting physiological properties of the individual. In normal adult RBC, Hb variants that exist are HbA1, HbA2, HbS and HbF. Mutations in globin chains can change the Hb-O2 affinity which can alter the normal loading of oxygen in lungs and unloading in the tissues and also affect arterial oxygen saturation. Absence of abnormal Hbs rules out upto some extent presence of genetic or acquired facilitated oxygen affinity. Methodology: The study was undertaken to compare haemoglobin variants using HPLC in Indians (n=10) and Kyrgyz population groups (n=10). We estimated oxygen affinity (P50) from PO2, SO2 and pH values using Lichtman equation and peripheral oxygen saturation (SpO2) using pulse oximetry at basal and upon acute HA exposure to 4111m in both the population groups. Results: We obtained Hb fractions A1a, A1b, A1c and A2 within normal range and no HbF or HbS fractions were found in any volunteer from HPLC run. All the P50 values were well within normal range (22-28mmHg). No change in P50 was observed upon HA exposure in these two populations but Kyrgyz have been found to have a higher P50 compared to Indians at basal. Discussion and Conclusion: Since our data rule-out the existence of abnormal Hb variant in either of the population, thus the significant decrease in SpO2 observed upon HA induction in both the groups is due to hypoxia at HA and higher P50 in Kyrgyz compared to Indians is population specific.