As anthropogenic activities directly and indirectly increase carbon dioxide (CO2) and decrease oxygen (O2) concentrations in the ocean system, it becomes important to understand how different populations of marine animals will respond. Water that is naturally low in pH, with a high concentration of carbon dioxide (hypercapnia) and a low concentration of oxygen, occurs at shallow depths (200–500 m) in the North Pacific Ocean, whereas similar conditions are absent throughout the upper water column in the North Atlantic. This contrasting hydrography provides a natural experiment to explore whether differences in environment cause populations of cosmopolitan pelagic calcifiers, specifically the aragonitic-shelled pteropods, to have a different physiological response when exposed to hypercapnia and low O2. Using closed-chamber end-point respiration experiments, eight species of pteropods from the two ocean basins were exposed to high CO2 ( ∼  800 µatm) while six species were also exposed to moderately low O2 (48 % saturated, or  ∼  130 µmol kg−1) and a combined treatment of low O2/high CO2. None of the species tested showed a change in metabolic rate in response to high CO2 alone. Of those species tested for an effect of O2, only Limacina retroversa from the Atlantic showed a response to the combined treatment, resulting in a reduction in metabolic rate. Our results suggest that pteropods have mechanisms for coping with short-term CO2 exposure and that there can be interactive effects between stressors on the physiology of these open ocean organisms that correlate with natural exposure to low O2 and high CO2. These are considerations that should be taken into account in projections of organismal sensitivity to future ocean conditions.