We investigate the temporal variability of oxygen in the upper water column of the North Pacific using a hindcast ocean model. The model embeds simple biogeochemical cycles of nutrients and O2 within an isopycnal circulation model that is forced at the surface by historical atmospheric conditions. The resulting O2 variability is spatially and temporally complex, but includes large-scale O2 decreases between the 1980s and 1990s in the subpolar region, and simultaneous O2 increases in the subtropics. These simulated changes are similar in pattern to those observed along repeat transects (Emerson et al., 2004), suggesting that the model captures key mechanisms of late twentieth century O2 variability in the North Pacific. Additional simulations were performed to distinguish O2 changes due to variability in biology, ventilation, and circulation. Regional trends in export production drive significant oxygen changes that are focused in the upper thermocline, where remineralization rates are largest. However, shallow biological O2 changes are often balanced by opposing physically driven O2 changes. In contrast, physical processes of ventilation and circulation are found to be the dominant cause of model O2 variability in the lower ventilated thermocline, where observed O2 anomalies are the largest. These results suggest that O2 variability in the lower ventilated thermocline may be a useful tracer of physical climate change in the North Pacific, while changes in the biological pump may be difficult to detect on the basis of O2 trends alone. Continued analysis of historical patterns of subsurface O2 variability will provide important further tests of these conclusions.