Background: Both high-altitude hypoxia and COVID-19 can independently induce cardiopulmonary dysfunction, with multiple pathophysiological intersections theoretically existing between the two. Methods: This cross-sectional study recruited 290 Han Chinese residents living in Lhasa, comprising 89 COVID-19 convalescents (COVID group) and 201 non-infected controls (N-COVID group). All participants underwent standardized cardiopulmonary exercise testing (CPET), muscle strength assessment, and completed the FACIT-Fatigue, IPAQ, and Pittsburgh Sleep Quality Index questionnaires. Results: No significant differences were observed between the COVID and N-COVID groups in age, height, body weight, BMI, duration of high-altitude residence, FACIT-Fatigue score, IPAQ score, or Pittsburgh Sleep Quality Index score (P > 0.05). Additionally, no significant between-group differences were found in FVC, FEV₁, VO₂peak, or VO₂peak/kg (P > 0.05). However, the COVID group demonstrated significantly elevated VE/VCO₂ (43.66±4.49VS40.92±4.40), VE/VCO₂ slope (43.18±5.95VS40.47±5.49), and RER (1.08±0.046VS1.06±0.046) compared to the N-COVID group ( P < 0.05). Furthermore, the N-COVID group exhibited significantly better grip strength and balance performance than the COVID group (P < 0.05). Conclusions: Ventilatory efficiency may serve as a more specific indicator for evaluating cardiopulmonary function in this population. Clinical assessment should not rely solely on traditional metrics such as VO₂peak. For rehabilitation, interventions targeting respiratory pattern training to improve ventilatory efficiency and proprioceptive training to enhance neuromuscular control are recommended.

High-altitude Hypoxia, Covid-19, Cardiopulmonary Exercise Testing, Ventilatory Efficiency, Oxygen Uptake