Accurate monitoring of the long-term trend of oxygen content at global scale requires a better knowledge of the regional oxygen variability at interannual to decadal time scale. Here, we combined the Argo dataset and repeated ship-based sections to investigate the drivers of the oxygen variability in the North Atlantic Ocean, a key region for the oxygen supply into the deep ocean. We focus on the Labrador Sea Water in the Irminger Sea over the period 1991–2018 and we show that the oxygen solubility explains less than a third of the oxygen variability. In turn, the main drivers of the oxygen variability are due to changes in vertical mixing, advection, and other processes as revealed by Apparent Oxygen Utilization computation. Our findings revealed the key role of physical processes on the changes in oxygen variability and highlight the need of keeping a sustained monitoring of those processes to disentangle human-induced changes in oxygen from decadal natural variability.