The brand, a sister company of American Cruise Lines, will deploy its 210-passenger Pearl Mist from Fort Lauderdale's Port Everglades.
The 10-night cruise will circumnavigate the island, visiting Havana and ports on the southern coast including Cienfuegos, Trinidad and Santiago de Cuba.
Pearl Seas Cruises has a cultural focus and said its people-to-people programs will be more personalized than those of larger ships.
'There is significant demand to visit Cuba on a smaller ship and we are honored to be among the first cruise lines to have access to the country,' Pearl Seas vp Timothy Beebe said.
The company plans 11 cruises from January through May. Each stretches 10 nights and sails round-trip Port Everglades.
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