This investigation sought to assess whether single or repeated bouts of ischemic preconditioning (IPC) could improve oxyhemoglobin saturation (SpO2) and/or attenuate reductions in muscle tissue saturation index (TSI) during submaximal hypoxic exercise. Fifteen healthy young men completed submaximal graded exercise under four experimental conditions: (1) normoxia (NORM), (2) hypoxia (HYP), FiO2 = 0.14, ~3200 m, (3) hypoxia preceded by a single session of IPC (IPC1-HYP), and (4) hypoxia preceded by seven sessions of IPC, one a day for seven consecutive days (IPC7-HYP). IPC7-HYP heightened VE at 80% HYP Wpeak (+10.47 ± 3.35 L·min-1, p= 0.006), compared to HYP, as a function of increased breathing frequency. Both IPC1-HYP (+0.17 ± 0.04 L·min-1, p< 0.001) and IPC7-HYP (+0.16 ± 0.04 L·min-1, p< 0.001) elicited greater VO2 across exercise intensities compared to NORM, while VO2 was unchanged with HYP alone. SpO2 was unchanged by either IPC condition at any exercise intensity. Yet, the reduction of muscle TSI during resting hypoxic exposure was attenuated by IPC7-HYP (+9.9 ± 3.6%, p= 0.040) compared to HYP, likely as a function of reduced local oxygen extraction. Considering all exercise intensities, IPC7-HYP attenuated reductions of TSI with HYP (+6.4 ± 1.8%, p= 0.001). Seven days of IPC heightens ventilation, posing a threat to ventilatory efficiency, during high intensity submaximal hypoxic exercise and attenuates reductions in hypoxic resting and exercise muscle oxygenation in healthy young men. A single session of IPC may be capable of modulating hypoxic ventilation, however, our current population was unable to demonstrate this with certainty.