Marine deoxygenation and anthropogenic ocean warming are observed and projected to intensify in the future. These changes potentially impact the functions and services of marine ecosystems. A key question is whether marine ecosystems are already or will soon be exposed to environmental conditions not experienced during the last millennium. Using a forced simulation with the Community Earth System Model (CESM) over the period 850 to 2100, we find that anthropogenic deoxygenation and warming in the thermocline exceeded natural variability in, respectively, 60 % and 90 % of total ocean area. Control simulations are typically used to estimate the pre-industrial variability level. However, the natural variability of oxygen (O₂) and temperature (...