Frontier currently offers nonstop flights to and from Denver two times per week: Thursday and Sunday.
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The news comes on the same day a $2.9 billion merger was announced between Frontier and Spirit Airlines, another so-called "ultra-low-cost carrier."
Frontier made a return back to the Fresno market in 2018 after a departure in 2007, and another in 2015.
A spokesperson with the airport called the move "a business decision."
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The spokesperson said in a statement that they don't have any information about how the merger between Spirit and Frontier could affect future service in Fresno.
Fresno Yosemite International Airport will continue to offer daily service to Denver on United and the airport's newest airline, Southwest.
Airport officials say it wouldn't be surprising to see the newly merged Frontier and Spirit make another comeback with different options.
Justin Kincy flies into the Central Valley for the Ag Expo every year and says he would love to see a flight from the midwest.
Last year, Fresno opened a new parking structure at the airport. Next up is an expanded terminal with more gates and more places to eat, an expanded baggage claim area and a reconfiguration to allow more seamless international service.
While the loss of Frontier is a step back for the airport, it comes after several big leaps forward with more to come.