Celebrity Millennium will cruise from 5 June with a vaccinated crew and adult guests.
Children under the age of 18 must show proof of a negative test result within 72 hours of embarkation.
Bookings open from 25 March with an Aruba, Curacao and Barbados itinerary and a voyage visiting Tortola, St Lucia and Barbados on offer.
Celebrity will also offer tours at each port of call and private small group excursions are available to explore destinations with only family members or those in the same travelling party.
Millennium, which has undergone a $500 million refurbishment as part of the Celebrity Revolution programme, will operate “comprehensive, multi-layered health and safety measures”, the line said.
Celebrity said its protocols - including vaccination requirements – would "evolve in keeping with current public health standards”.
In addition, guests must meet St. Maarten’s entry requirements, which currently include a negative PCR test taken within 72-hours of arrival to the island.
Celebrity Cruises president and chief executive, Lisa Lutoff-Perlo, called the line’s return to the Caribbean after more than a year away was “such a significant moment”.
“It marks the measured beginning of the end of what has been a uniquely challenging time for everyone. We have been in constant contact with the leadership of St. Maarten these past months to support each other and share learnings and best practices," she said.
“That we’re able to offer people the opportunity to safely holiday onboard the revolutionised Celebrity Millennium, is incredible, and that we will sail from the magical island of St. Maarten is very special. I am forever grateful for the support and collaboration of the St. Maarten government.”
