The line cited a "lack of availability of charter aircraft on Caribbean routes" for its decision.
The move affects all seven and 14-night fly-cruises onboard Britannia, starting and ending in Saint Lucia, which were due to depart between October 2021 and March 2022.
P&O’s Barbados fly-cruise programme is scheduled to go ahead as planned, said P&O on its website.
"Due to Covid-19 protocols, we are not permitted to allow guests on board who have taken scheduled flights to St Lucia," said P&O.
"Therefore, this will no longer be a turnaround port for boarding or disembarking guests."
Guests booked on affected cruises were notified by email on Tuesday (27 July) or by post, and have been offered a future cruise credit incentive.
Those wishing to apply for a full refund must do so before the end of the year.
