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Pine Island Sound is located in Lee County, Florida, lying between Pine Island (Lee County, Florida) and the barrier islands of Sanibel Island, Captiva Island, North Captiva Island and Cayo Costa, which separate the Sound from the Gulf of Mexico. The Sound connects to Gasparilla Sound andCharlotte Harbor to the north, and to San Carlos Bay and the Caloosahatchee River to the south. The Sound is conterminous with the Pine Island Sound Aquatic Preserve, which was established in 1970 and consists of 54,000 acres (220 km²) of submerged land. Important habitats in the Sound include mangroves, seagrasses, salt marshes, oyster communities and tidal flats.
For thousands of years, the sound was home to the Calusa Indians and their ancestors. In the 18th and 19th centuries it was an important winter fishery for the Cuban mullet fleet. In the early 1960s, in preparation for the Bay of Pigs Invasion, the CIA trained some Cuban exiles on Useppa Island, located in the center of the sound.