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Cayo Guilermo is a tropical island in the Jardines Del Ray archipelago. It is located on the northern coast of Cuba, between the Bay of Dogs (Bahia de Perros) and the Atlantic Ocean. It is part of the Ciego de Ávila Province and lies in the Morón municipality.

The island is a popular tourist destination, just east of the resort by the causeway to Cayo Coco is a marina used by yachts, sport fishing, and tour boats. One of the country's best beaches, the Playa Pilar (Pilar Beach) is located at the western end of Cayo Guillermo.