The Looe Key National Marine Sanctuary was a National Marine Sanctuary in the waters in the Florida Keys in Florida in the United States. It protected Looe Key, a coral reef south of Big Pine Key, and had an area of 5.32 square nautical miles (7.05 sq mi; 18.2 km). It was among three national marine sanctuaries designated on January 16, 1981, expanding the national marine sanctuary system from three to six sanctuaries. The Florida Keys National Marine Sanctuary subsumed the Looe Key National Marine Sanctuary when it was designated on December 28,1990.