Budget carrier Easyjet plans to pull out of Doncaster Sheffield airport from January 4 next year.
Nick Smillie, aviation sales director for Peel Airports, which owns and operates Robin Hood Doncaster Sheffield airport, said he is "disappointed".
"Operational restrictions, largely due to the fact that the aircraft is not Doncaster based, have affected the viability of the operation," said Smillie.
Bad timings for flights to key business travel destinations have "affected the attractiveness to the region's business community - a key source of passengers and revenues", he said.
For example, the flight to Amsterdam leaves at 1.05pm, arriving into Amsterdam at 4.05pm, the end of the business day.
Easyjet also currently flies from Doncaster Sheffield to Barcelona, Faro, Majorca and Prague.
Smillie said the airport is in talks with airlines to re-instate the routes.
An Easyjet spokeswoman told ABTN the one aircraft currently operated out of Doncaster Sheffield will be moved to Liverpool airport.