We explore centennial changes in tropical Pacific oxygen (O-2) using numerical models to illustrate the dominant patterns and mechanisms under centennial climate change. Future projections from state-of-the-art Earth System Models exhibit significant model to model differences, but decreased solubility and weakened ventilation together deplete thermocline O-2 in middle to high latitudes. In contrast, the tropical thermocline O-2 undergoes much smaller changes or even a slight increase. A suite of sensitivity experiments using a coarse resolution ocean circulation and biogeochemistry model show that ocean warming is the leading cause of global deoxygenation in the thermocline across all latitudes with secondary contributions from changes in hydrological cycles and wind stress modulating regional changes in O-2. The small O-2 changes in the tropical Pacific thermocline reflect near-complete compensation between the solubility decrease due to warming and reduction in apparent oxygen utilization (AOU). We further quantified the changes in AOU due to contributions from changes in water mass age and biological remineralization from the sensitivity experiments. The two effects almost equally contribute to the reduction of AOU in the tropical Pacific thermocline (43% for physical circulations and 57% for biology). Our results suggest that better understanding of water mass changes in the tropical oceans is key to improving projections and reducing the uncertainties of future O-2 changes. Plain Language Summary Global warming in the next hundred years could lead to a large amount of oxygen loss from the ocean. This could impact not only the marine ecosystem but also fisheries. We use model simulations to investigate how long-term climate change, such as changes in sea surface temperature, precipitation, and winds, under the anthropogenic transient could impact oceanic oxygen loss in the next hundred years. The ocean loses oxygen in most of the regions but tropical oceans could actually gain oxygen regionally. We investigate what causes these unique oxygen changes in the tropical Pacific Ocean. The counterintuitive oxygen changes in the tropical Pacific Ocean are likely due to, by an almost equal amount of effects, changes in water mass supply due to changes in circulations and changes in biological activity, that is, consumption of oxygen through respiration. Tropical oceans are sensitive to oxygen loss because of its impact on marine ecosystems. Our study could provide a better understanding of future oxygen loss in the ocean.