Climate change and changing nutrient loadings are the two main aspects of global change that are linked to the increase in the prevalence of coastal hypoxia – the depletion of oxygen in the bottom waters of coastal areas. However, it remains uncertain how strongly these two drivers will each increase the risk of hypoxia over the next decades. Through model simulations we have investigated the relative influence of climate change and nutrient run-off on the bottom water oxygen dynamics in the Oyster Grounds, an area in the central North Sea experiencing summer stratification. Simulations were performed with a one-dimensional ecosystem model that couples hydrodynamics, pelagic biogeochemistry and sediment diagenesis. Climatological conditions for the North Sea over the next 100 yr were derived from a global-scale climate model. Our results indicate that changing climatological conditions will increase the risk of hypoxia. The bottom water oxygen concentration in late summer is predicted to decrease by 24 μM or 11.5% in the year 2100. More intense stratification is the dominant factor responsible for this decrease (58%), followed by the reduced solubility of oxygen at higher water temperature (27%), while the remaining part could be attributed to enhanced metabolic rates in warmer bottom waters (15%). Relative to these climate change effects, changes in nutrient runoff are also important and may even have a stronger impact on the bottom water oxygenation. Decreased nutrient loadings strongly decrease the probability of hypoxic events. This stresses the importance of continued eutrophication management in coastal areas, which could function as a mitigation tool to counteract the effects of rising temperatures.