Coastal ecosystems worldwide are under pressure from human-induced nutrient inputs, fishing activities, mariculture, construction work, and climate change. Integrated management instruments handling one or more of these problems in combination with socioeconomic issues are therefore necessary to secure a sustainable use of resources. In the Limfjord, a temperate eutrophic estuary in Denmark, nutrient load reductions are necessary to fulfill EU regulations such as the Water Framework Directive (WFD). The expected outcome of these load reductions is an improved water quality, but also reduced production of the abundant stock of filter-feeding blue mussels, Mytilus edulis. This is expected to have significant economic consequences for the million-euro mussel fishing industry taking place in the Limfjord today. We developed a bioeconomic model that can be used to explore the consequences of load reductions for mussel fishery as practiced today, as well as potential management options, to obtain an economically and ecologically sustainable mussel fishery. Model simulations clearly demonstrate a substantial decrease in mussel production after the nutrient load reductions necessary to obtain the targets in the WFD. With today’s practice, the mussel fishery in the Limfjord will not be profitable in a future, less eutrophic estuary. However, model simulations also revealed that mussel fishery can be profitable after implementation of the WFD with a reduction in the total fishing quota, fewer fishing vessels, and a higher fishing quota per vessel.