Marine Spatial Planning (MSP) provides a process that uses spatial data and models to evaluate environmental, social, economic, cultural, and management trade-offs when siting ocean industries. Aquaculture is the fastest-growing food sector in the world. The U.S. has substantial opportunity for offshore aquaculture development given the size of its exclusive economic zone, habitat diversity, and variety of candidate species for cultivation. However, many protected species rely upon habitats that overlap with promising aquaculture areas. Siting surveys, farm construction, operations, and decommissioning can alter the habitat and behavior of animals in the vicinity of these activities. Vessel activity, underwater noise, and physical interactions between protected species and farms can potentially increase the risk of injury or cause direct mortality. In 2020, the U.S. Gulf of Mexico was identified as one of the first regions to be evaluated for offshore aquaculture opportunities as directed by a Presidential Executive Order. We developed a generalized scoring model for protected species data layers that captures vulnerability using species conservation status and demographic information. We applied this approach to data layers for eight species listed under the Endangered Species Act, including five species of sea turtles, Rice’s Whale, Smalltooth Sawfish, and Giant Manta Ray. We evaluated several methods for scoring (e.g., arithmetic mean, geometric mean, product, lowest scoring layer) and created a combined protected species data layer that was used within a multi-criteria decision-making modeling framework for MSP. The product approach for scoring provided the most logical ordering of and the greatest contrast in site suitability scores. This approach provides a transparent and repeatable method to identify aquaculture site alternatives with the least conflict with protected species. These modeling methods are transferable to other regions, to other sensitive or protected species, and for spatial planning for other ocean-uses.