In the setting of “living high,” it is unclear whether high-intensity interval training (HIIT) should be performed “low” or “high” to stimulate muscular and performance adaptations. Therefore, 10 physically active males participated in a 5-week “live high-train low or high” program (TR), whilst eight subjects were not engaged in any altitude or training intervention (CON). Five days per week (~15.5 h per day), TR was exposed to normobaric hypoxia simulating progressively increasing altitude of ~2,000–3,250 m. Three times per week, TR performed HIIT, administered as unilateral knee-extension training, with one leg in normobaric hypoxia (~4,300 m; TRHYP) and with the other leg in normoxia (TRNOR). “Living high” elicited a consistent elevation in serum erythropoietin concentrations which adequately predicted the increase in hemoglobin mass (r = 0.78, P < 0.05; TR: +2.6%, P < 0.05; CON: −0.7%, P > 0.05). Muscle oxygenation during training was lower in TRHYP vs. TRNOR (P < 0.05). Muscle homogenate buffering capacity and pH-regulating protein abundance were similar between pretest and posttest. Oscillations in muscle blood volume during repeated sprints, as estimated by oscillations in NIRS-derived tHb, increased from pretest to posttest in TRHYP (~80%, P < 0.01) but not in TRNOR (~50%, P = 0.08). Muscle capillarity (~15%) as well as repeated-sprint ability (~8%) and 3-min maximal performance (~10–15%) increased similarly in both legs (P < 0.05). Maximal isometric strength increased in TRHYP (~8%, P < 0.05) but not in TRNOR (~4%, P > 0.05). In conclusion, muscular and performance adaptations were largely similar following normoxic vs. hypoxic HIIT. However, hypoxic HIIT stimulated adaptations in isometric strength and muscle perfusion during intermittent sprinting.