Expansion of oxygen deficient waters (hypoxia) in the northeast Pacific Ocean (NEP) will have marked impacts on marine life. The response of the resident communities will be a function of their ecophysiological constraints in low oxygen, although this remains untested in the NEP due to a lack of integrative studies. Here, we combine in situ surveys and lab-based respirometry experiments were conducted on three indicator species (spot prawn Pandalus platyceros, slender sole Lyopsetta exilis, squat lobster Munida quadrispina) of seasonally hypoxic systems in the NEP to test if metabolic constraints determine distributions and energy sequestration in a hypoxic setting. These experiments were integrated with a global review of critical oxygen levels ( math formula; lower threshold of aerobic metabolism) for crustaceans to determine if math formula-based hypoxia thresholds are different among ocean basins. Our results show that species-specific differences in math formula and standard metabolic rates (1) determine the lowest environmental oxygen ([O2]env) at which in situ populations occur, (2) result in disproportionate shifts in distributions among co-occurring species during summer hypoxia expansion events, and (3) characterize shifts in megafaunal community respiration rates due to marked spatio-temporal variability in [O2]env. Our results show that math formula-based hypoxia thresholds are significantly lower in the East Pacific Ocean relative to other major ocean basins, which suggests that the physiological response of local fauna to deoxygenation can be determined by the natural variability and oxygen exposure in a region. In order to establish realistic predictions on the biological consequences of marine deoxygenation, we suggest integrating metabolism-based traits to calculate hypoxia thresholds for marine ecosystems.