The pelagic octopod Japetella diaphana inhabits meso- and bathypelagic depths worldwide. Across its geographic and depth range, individuals encounter oxygen levels ranging from nearly air-saturated to nearly anoxic. In this study, we assessed the physiological adaptations of individuals from one of the largest and most extreme regions of ocean hypoxia, the Eastern Tropical North Pacific (ETNP) oxygen minimum zone (OMZ). Ship-board measurements of metabolic rate and hypoxia tolerance were conducted and a metabolic index was constructed to model suitable habitat for aerobic metabolism. We found that individuals from the ETNP had a low metabolic rate, yet higher than conspecifics from more oxygen-rich habitats. Despite their higher rates, hypoxia tolerance may be similar to or greater than in conspecifics from more oxygen-rich waters. Furthermore, hypoxia tolerance in J. diaphana has a reverse temperature-dependence from most marine ectotherms, a characteristic that uniquely suits the physical characteristics of the lower oxycline. Even with its high tolerance to hypoxia, J. diaphana is incapable of maintaining basal oxygen demand in the OMZ core, at a depth where populations are typically most abundant in more oxygenated regions. Despite the limited metabolically-suitable habitat, J. diaphana is abundant in the ETNP outside the OMZ core, suggesting that physiological and behavioral plasticity is sufficient to maintain species fitness in this region.