Spatio-seasonal explicit simulation models can predict the impact of spatial management measures on marine fish populations and fishing activities. As fisheries are complex systems, fisheries simulation models are often complex, with many uncertain parameters. Here, the methodology is provided to deliver fishery diagnostics within an uncertainty context using a complex simulation tool. A sensitivity analysis of the model is performed on model outputs using partial least-squares to identify the most sensitive parameters. The impact of several management measures is then simulated using a statistical simulation design taking into account the uncertainty of the selected sensitive parameters. This approach was applied to the Bay of Biscay anchovy stock using the ISIS-Fish (Integration of Spatial Information for Simulation of Fisheries) model to assess the impact of imposing marine protected areas (MPAs) conditionally on parameter uncertainty. The diagnostic appeared to be highly sensitive to the mortality of larvae and juveniles, growth, and reproduction. The uncertainty of the values of these parameters did not permit any of the simulated MPA designs to be proposed. However, according to anchovy catch and biomass, the simulations allowed the low impact of closure duration to be shown and underscored the utility of protecting such key processes as spawning.