Protective masks impose variable breathing resistance (BR) on the wearer and may adversely affect exercise performance, yet existing literature shows inconsistent results under different types of masks and metabolic demands. The present study was undertaken to determine whether added BR impairs cardiopulmonary function and aerobic performance during exercise. Sixteen young healthy men completed a graded exercise test on a cycle ergometer under the four conditions of BR using a customized breathing resistor at no breathing resistance (CON), 18.9 (BR1), 22.2 (BR2), and 29.9 Pa (BR3). The results showed that BR significantly elevates respiratory pressure ( < 0.001) and impairs ventilatory response to graded exercise (reduced V ; < 0.001) at a greater degree with an increased level of BR which caused mild to moderate exercise-induced hypoxemia (final mean SpO : CON = 95.6%, BR1 = 94.4%, BR2 = 91.6%, and BR3 = 90.6%; < 0.001). Especially, such a marked reduction in SpO was significantly correlated with maximal oxygen consumption at the volitional fatigue (r = 0.98, < 0.001) together with exaggerated exertion and breathing discomfort ( < 0.001). In conclusion, added BR commonly experienced when wearing tight-fitting facemasks and/or respirators could significantly impair cardiopulmonary function and aerobic performance at a greater degree with an increasing level of BR.