Travel company Tui said it has cancelled flights out of Luton Airport because it falls under the new tier four Covid restrictions.
Tui flights from the London airport are cancelled between 20 and 30 December.
It said: "We will be in direct contact with these customers to offer them a full refund or the option to amend their booking."
Tui will continue to operate out of Gatwick and Stansted which are located in tier two areas.
A company spokesperson said: "Any customers that live in tier four and are due to depart in the next 14 days will be entitled to cancel and receive a full refund or amend for free to any holiday that's currently on sale."
Luton, Heathrow and London City airports are all located in areas of England facing the toughest restrictions under measures aimed at stopping the spread of a new coronavirus variant.
A number of European countries are banning or considering stopping flights from the UK following the emergence of a new variant of the virus.
Italy has joined the Netherlands and Belgium in suspending flights to the UK, and other nations are considering the move.
Trains to Belgium have also been banned.
The government is recommending that people living in tier four regions should not travel abroad unless for legally permitted reasons such as for work.
People living outside a tier four area are allowed to journey through that area if they are travelling abroad but the government said: "You should carefully consider whether you need to do so."
Easyjet, which operates out of Luton, said it was planning to fly its current schedule over the coming days.
"However, following the UK government's announcement implementing tier four restrictions which includes advice against travelling abroad, we understand some customers may now need to change their flights," the airline said.
It said affected customers can transfer to an alternative flight free of charge, receive a voucher or can opt for a refund for any flight up until 30 December.
Easyjet also flies out of Gatwick and Stansted.
Stansted is in Uttlesford, Essex, which has been kept in lower tier two restrictions. Gatwick is in Crawley, west Sussex, which also remains under tier two.
Virgin Atlantic, which operates out of London Heathrow, said: "Where a customer is unable to travel for any reason, we offer as much choice and flexibility as possible to help them change or amend their plans, with a name change and two date change fees waived for a new travel date up until 31 December 2022.
"Where a flight is cancelled, customers are of course entitled to a full cash refund."
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