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Objectives: In this study, we measured the hematologic and spirometric parameters of native Tajik and Kyrgyz highlanders in the Pamir Mountains to investigate adaptations to high altitude stressors. Methods: Hematological parameters including arterial oxygen saturation (SaO2), red blood cell (RBC) counts, and hemoglobin (Hb) concentration were measured on Sarikoli Tajik (n = 80; 3100 m), Wakhi Tajik (n = 48; 3500 m), and Kyrgyz (n = 64; 3250 m) in comparison to lowland Uyghurs (n = 50; 1300 m). Spirometric parameters including forced vital capacity (FVC), the first second of forced expiration (FEV1), and forced expiratory flow between 25% and 75% (FEF25‐75) were measured. We also reported mountain sickness symptoms in these highlanders and conducted a multivariate regression analysis to analyze the association between these symptoms and the measured parameters. Results: SaO2 of Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (91%‐93.5%) are significantly lower than lowland Uyghurs, yet are comparable to other native highlanders at a similar altitude. RBC counts and Hb concentrations of all three highland populations are significantly increased compared to Uyghurs. FVC is lower in Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (male: 3.48‐3.86 L, female: 2.47‐2.78 L) compared to Uyghurs. Combined with normal FEV1, elevated FEV1/FVC ratio, and FEF25‐75, the spirometric patterns of these highlanders indicate restrictive lung disease. A high prevalence of mountain sickness symptoms such as headache and nausea was found in all three highland populations, and are attributed to low FVC and aging by regression analysis. Conclusion: Tajik and Kyrgyz highlanders showed adaptation in SaO2, RBC, and Hb level, but poor performance in spirometry, which causes mountain sickness. [ABSTRACT FROM AUTHOR]