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The Mediterranean region is a climate change hotspot. Increasing greenhouse gas emissions are projected to lead to a substantial warming of the Mediterranean Sea as well as major changes in its circulation, but the subsequent effects of such changes on marine biogeochemistry are poorly understood. Here, our aim is to investigate how climate change will affect nutrient concentrations and biological productivity in the Mediterranean Sea. To do so, we perform transient simulations with the coupled high-resolution model NEMOMED8-PISCES using the high-emission IPCC Special Report on Emissions Scenarios (SRES) A2 socioeconomic scenario and corresponding Atlantic, Black Sea, and riverine nutrient inputs. Our results indicate that nitrate is accumulating in the Mediterranean Sea over the 21st century, while phosphorus shows no tendency. These contrasting changes result from an unbalanced nitrogen-to-phosphorus input from riverine discharge and fluxes via the Strait of Gibraltar, which lead to an expansion of phosphorus-limited regions across the Mediterranean. In addition, phytoplankton net primary productivity is reduced by 10% in the 2090s in comparison to the present state, with reductions of up to 50% in some regions such as the Aegean Sea as a result of nutrient limitation and vertical stratification. We also perform sensitivity tests to separately study the effects of climate and biogeochemical input changes on the future state of the Mediterranean Sea. Our results show that changes in nutrient supply from the Strait of Gibraltar and from rivers and circulation changes linked to climate change may have antagonistic or synergistic effects on nutrient concentrations and surface primary productivity. In some regions such as the Adriatic Sea, half of the biogeochemical changes simulated during the 21st century are linked with external changes in nutrient input, while the other half are linked to climate change. This study is the first to simulate future transient climate change effects on Mediterranean Sea biogeochemistry but calls for further work to characterize effects from atmospheric deposition and to assess the various sources of uncertainty.