Air Wales announced on Friday evening that it is to pull out of all flights from Plymouth Airport.
Air Wales will stop flights on 20 February
The change will take effect later this month. The small Cardiff-based airline ceased its flights from Plymouth to Dublin last month.
At Christmas, passengers were left stranded in Plymouth when the plane they thought they were booked on failed to turn up.
Flights to Cardiff, Aberdeen and Newcastle will stop on 20 February.
Passengers who have booked on services after that will either be offered flights on alternative carriers, or refunds.