Ocean acidification is hypothesized to limit the performance of squids due to their exceptional oxygen demand and pH-sensitivity of blood-oxygen binding, which may reduce oxygen supply in acidified waters. The critical oxygen partial pressure (Pcrit), the PO2 below which oxygen supply cannot match basal demand, is a commonly reported index of hypoxia tolerance. Any CO2-induced reduction in oxygen supply should be apparent as an increase in Pcrit. In this study, we assessed the effects of CO2 (46-143 Pa; 455-1410 μatm) on the metabolic rate and Pcrit of two squid species - Dosidicus gigas and Doryteuthis pealeii - through manipulative experiments. We also developed a model, with inputs for hemocyanin pH-sensitivity, blood PCO2, and buffering capacity that simulates blood oxygen supply under varying seawater CO2 partial pressures. We compare model outputs to measured Pcrit in squids. Using blood-O2 parameters from the literature for model inputs, we estimated that, in the absence of blood acid-base regulation, an increase in seawater PCO2 to 100 Pa (≈ 1000 μatm) would result in a maximum drop in arterial hemocyanin-O2 saturation by 1.6% at normoxia and a Pcrit increase of ≈0.5 kPa. Our live-animal experiments support this supposition, as CO2 had no effect on measured metabolic rate or Pcrit in either squid species.