Much of the CO₂ released by human activity into the atmosphere is dissolving into the oceans, making them more acidic. In this study we provide the first data on the short- and long-term impacts of ocean acidification on octopuses. We measured routine metabolic rate (RMR) of Octopus rubescens at elevated CO₂ pressure (Pco₂) with no prior acclimation and 1 or 5 wk of acclimation and critical oxygen pressure (P_crit) after 5 wk of acclimation. Our results show that with no prior acclimation, octopuses had significantly higher RMRs in 1,500-μatm Pco₂ environments than octopuses in 700- or 360-μatm environments. However, after both 1 and 5 wk of acclimation there was no significant difference in RMRs between octopuses at differing Pco₂, indicating that octopuses acclimated rapidly to elevated Pco₂. In octopuses acclimated for 5 wk at 1,500 μatm Pco₂, we observed impaired hypoxia tolerance, as demonstrated by a significantly higher P_crit than those acclimated to 700 μatm Pco₂. Our findings suggest that O. rubescens experiences short-term stress in elevated Pco₂ but is able to acclimate over time. However, while this species may be able to acclimate to near-term ocean acidification, compounding environmental effects of acidification and hypoxia may present a physiological challenge for this species.