Durham Tees Valley airport have announced they are "moving away" from mainstream holiday charter programmes from summer 2014.
Tour operators affected are Thompson/First Choice and Balkan Holidays.
Flights to Schipol in Amsterdam, operated by KLM, and Aberdeen, operated by Eastern Airways, will not be affected.
Flybe flights operated on behalf of CITS to Jersey will also remain in place.
Anyone who has booked holiday flights to Palma, Ibiza or Bulgaria for 2014 flying from Durham Tees Valley Airport is advised to contact their tour operator or travel agent for advice.
Travel expert Simon Calder says once passengers have been to airports like Newcastle, Bradford and Manchester, it is difficult to lure them back.
Durham Tees Valley Airport is to make an announcement about its future later today. It follows yesterdays announcement that Thomson and First Choice had been told they wouldn't be able to operate flights from the airport next year.
Two charter flight operators are pulling out of Durham Tees Valley airport from next year after the airport's owners told them they can no longer operate from the site.
A spokesman for the airport said people who have already booked their seats will fly from another airport.
Thomson and First Choice will no longer be running flights from Durham Tees Valley Airport. They have given the following advice to customers:
"We can confirm that there will be no flights to Palma and Ibiza operated by Thomson Holidays from Durham Tees Valley Airport for the summer 2014 season. For alternative flights to these destinations customers are asked to consult the Thomson website. Further information on the future business direction of the airport will be announced shortly."
Following the news that Thomson and First Choice will no longer provide flights from Tees Valley Airport, Thomson has released this statement:
"Following a business review of operations by Durham Tees Valley Airport, Thomson and First Choice have been notified that they will no longer be able to operate their flights from the airport.
"We have therefore suspended flights from Durham Tees Valley Airport for Summer 2014. We would like to reassure those customers who have already booked holidays departing from Durham Tees Valley that they will be offered an alternative choice of airport.
Our customers are our number one priority and we apologise for any inconvenience caused by this change that is beyond our control. "
Thomson and First Choice will no longer be able to operate flights from Durham Tees Valley Airport.
Bosses at Durham Tees Valley Airport are to open a consultation on a blueprint for the site's future.
The airport, which has twice failed to secure government funding for its expansion, has now bought land it says could be used for "engineering, storage and distribution operations".
Owner Peel Holdings has said the proposals would safeguard some of the airport's flights.
Thomson has announced it will provide a weekly service from Durham Tees Valley Airport to Ibiza in summer 2014Read the full story ›
Durham Tees Valley Airport is set to become a centre for the storage and dismantling of unused aeroplanes.
Sycamore Aviation has set up its base at the airport and has already begun work on taking apart a number of airliners.
It is hoped that today's announcement will secure a financial future for the airport - which in the last five years has seen a reduction in both tourist destinations and passenger numbers.