Abstract End-to-end ecosystem modeling platforms, including OSMOSE, are key tools for informing ecosystem-based fisheries management (EBFM). End-to-end models ideally implement two-way interactions between model components, yet two-way interactions between high trophic level (HTL) functional groups and humans (fisheries managers and fishers) are currently missing in OSMOSE. We developed a management strategy evaluation (MSE) framework for OSMOSE, which allows for feedback between HTL functional groups and fisheries managers. This framework couples OSMOSE to a management procedure integrating decision rules and accounting for scientific uncertainty and the acceptable risk of overfishing. We applied the MSE framework to the OSMOSE model of the West Florida Shelf, so as to conduct an evaluation of total allowable catch (TAC) strategies for red grouper ( Epinephelus morio ) in a context of episodic events of natural mortality. Our simulations indicate that TAC strategies that assume higher scientific uncertainty and/or lower acceptable risk of overfishing result in higher biomass-related metrics for red grouper. However, the levels of scientific uncertainty and acceptable risk of overfishing impose a trade-off between biomass-related and catch-related metrics for red grouper. Our simulations also indicate that updating red grouper TAC more frequently in a context of episodic events of natural mortality does not have a large impact on biomass-related and catch-related metrics for red grouper and other functional groups. The MSE we conducted for red grouper is strategic, and its outcomes, which were obtained under a specific set of assumptions, must be considered preliminary. We discuss how future research could help enhance understanding of the possible impacts of TAC strategies for red grouper. The MSE framework designed for OSMOSE links the dynamics of HTL functional groups to that of fisheries managers, thereby allowing OSMOSE to be better suited for informing EBFM. This framework is an invaluable asset in assessing the performance of fisheries management strategies, but could also be used for other purposes, such as the evaluation of research monitoring programs.