Background: We compared acute psychophysiological responses with a single intermittent hypoxic exposure (IHE)/normoxic exposure trial with varying cycle lengths in adults with obesity. Materials and Methods: Eight obese adults (body mass index = 33.0 ± 2.2 kg/m2) completed three 60-minute IHE trials (passive seating), separated by 7 days. Trials comprised 30-minute hypoxia/30-minute normoxia (inspired oxygen fraction = 12.0%/20.9%) over Short (15 × 2/2 minutes), Medium (10 × 3/3 minutes), and Long (5 × 6/6 minutes) hypoxic/normoxic cycles and a control trial (60-minute normoxia). Results: Arterial oxygen saturation was lower during hypoxic periods of Long versus Medium and Short trials (90.1% vs. 93.0% and 94.2%; p = 0.02 and p = 0.05), with no differences between Short and Medium. Prefrontal cortex oxygenation was lower (-5.1%) during all IHE interventions versus control (p < 0.02), independent of cycle length. Perceived breathlessness was unaffected during IHE but increased 15 minutes after exposure versus baseline (+34%; p = 0.04). Breathlessness was lowest after Short versus control from 15 to 60 minutes (-7%; p = 0.01). Conclusions: When implementing IHE, greater desaturation is observed during longer compared with shorter hypoxic/normoxic cycles in adults with obesity. However, IHE tends to be better tolerated perceptually with shorter rather than longer cycles.