Mesopelagic fishes are a vital component of the biological carbon pump and are, to date, largely unexploited. In recent years, there has been an increased interest in harvesting the mesopelagic zone to produce fish feed for aquaculture. However, great uncertainties exist in how the mesopelagic zone interacts with the climate and food webs, presenting a dilemma for policy. Here, we investigate the consequences of potential policies relating to mesopelagic harvest quotas with a dynamic social-ecological modeling approach, combining system dynamics and global sensitivity analyses informed by participatory modeling. Our analyses reveal that, in simulations of mesopelagic fishing scenarios, uncertainties about mesopelagic fish population dynamics have the most pronounced influence on potential outcomes. The analysis also shows that prioritizing the development of the fishing industry over environmental protection would lead to a significantly higher social cost of climate change to society. Given the large uncertainties and the potential large impacts on oceanic carbon sequestration, a precautionary approach to developing mesopelagic fisheries is warranted.