Designated wilderness, Cedar Keys National Wildlife Refuge is primarily managed as part of the natural coastal environment. On occasion, prescribed burns may be conducted and exotic plants such as Brazilian pepper may be removed.
Bird and wildlife surveys are conducted on various Refuge islands to gather use and trend data for wildlife species.
Visitor services are focused on Atsena Otie Key to provide as much protection as possible to the remaining islands.
A lease agreement with the University of Florida allows for the operation of a Marine Science Lab on Seahorse Key. Other than special events hosted one to two times per year, the interior of the island is closed to all public entry.