The oxygen concentration in the ocean is controlled by a delicate balance between the source from atmosphere-ocean interaction and net respiration of organic matter after the water leaves the surface and descends into the interior. Fossil fuel-induced warming is predicted in global circulation models to decrease both the subsurface oxygen concentration and the downward flux of organic carbon from the ocean’s euphotic zone, with strong geographic variability in the responses of both. Oxygen concentrations have declined over the past 50 years in the few locations in the ocean thermocline where accurate long-term measurements exist. These observations are not, however, sufficiently widespread to determine global geographic variability nor long enough in duration to discern whether natural variations or anthropogenic effects cause these trends. Our challenge is to understand the mechanisms controlling oxygen concentration and to verify the carbon and oxygen cycle feedbacks predicted in global climate models. The cornerstone for achieving this goal is to obtain global coverage of accurate seasonal oxygen measurements in the ocean. It may be possible to do this by augmenting shipboard hydrographic studies with remote measurements of oxygen concentration using profiling floats, gliders, and moorings.