[Purpose] This study aimed to determine the systemic and peripheral responses to high-intensity interval exercise (HIIE) with voluntary hypoventilation at low lung volume (VHL) or HIIE under hypoxic conditions.[Methods] Ten male participants completed a single session of HIIE (three sets of 6 × 8-s high-intensity pedaling at 170% of maximal oxygen uptake [VO<sub>2max</sub>]) under three different conditions: normoxia with normal breathing (NOR: 23 °C, 20.9% of fraction of inspired oxygen [FiO<sub>2</sub>]), hypoxia with normal breathing (HYP: 23 °C, 14.5% FiO<sub>2</sub>), and normoxia with VHL (VHL: 23 °C, 20.9% FiO<sub>2</sub>). A randomized crossover design was used. Power output, arterial oxygen saturation (SpO<sub>2</sub>), heart rate, and muscle oxygenation were monitored during the exercise and the 16-s recovery. Muscle blood flow (mBF) of the vastus lateralis was also evaluated.[Results] SpO<sub>2</sub> during the exercise and the 16-s recovery in the VHL group was significantly lower than in that of the NOR group. However, this parameter in the VHL group was significantly higher than that of the HYP group (NOR: 94.9 ± 0.4%, HYP: 82.8 ± 1.2%, VHL: 90.4 ± 0.5%; <i>p</i> < 0.001). Muscle oxygen saturation was significantly lower in the HYP group than those in the VHL and NOR groups (NOR: 79.6 ± 17.4%, HYP: 65.5 ± 7.7%, VHL: 74.4 ± 7.8%; <i>p</i> = 0.024). No significant difference in this parameter was observed between the VHL and NOR groups (<i>p</i> > 0.05). Additionally, the exercise-induced increase in mBF did not differ significantly among three groups (<i>p</i> > 0.05).[Conclusion] HIIE-induced SpO<sub>2</sub> decrease was smaller under hypoxic conditions than during VHL. Moreover, mBF was not enhanced by the addition of VHL during HIIE.