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Applegate has left "Up All Night." Reuters

Will “Up All Night” hit the network chopping block sooner than expected?

On Friday, Deadline reported that the show’s star Christina Applegate is exiting the comedy.

In a statement, the actress cited so-called creative differences as the reason for her departure.

“It’s been a great experience working on ‘Up All Night,’ but the show has taken a different creative direction and I decided it was best for me to move on to other endeavors,” Applegate said. “Working with Lorne Michaels has been a dream come true and I am grateful he brought me into his TV family. I will miss the cast, producers and crew, and wish them the best always.”

Applegate’s costar, Will Arnett, commented on the news in a Twitter post.

On Saturday he tweeted, “Looks like I may be needing a new wife on @NBCUpAllNight. Any takers?”

Some believe that “Up All Night” is as good as cancelled following the 41-year-old’s exit.

Though “The Office” continued to air for two years after Steve Carell departed and “Two and a Half Men” is still running despite the absence of Charlie Sheen, both of those sitcomes had a loyal following to begin with. "Up All Night," not so much.

Despite rumors that Lisa Kudrow could replace the former “Married With Children” star, the show’s prospects are pretty grim.

“Up All Night” has been battling poor ratings since it premiered in September 2011.

Produced by Lorne Michaels, the series’ reception may be compared to that of “30 Rock” and “Parks and Recreation.”

Both shows battled low ratings despite critical acclaim and though neither show reached the top of the Neilson charts, online streaming sites like Hulu and Netflix have earned them a following.

“Up All Night,” which also stared Maya Rudolph, was set to undergo questionable format changes.

In October it was announced that the series would be shot in front of a live studio audience—abandoning its single-camera format.

The show is currently on hiatus and slated to return in April or May. As Deadline notes, none of the live episodes had been shot prior to Applegate leaving.

So were the show’s structural changes the reason for her exit?

The star has proven to be a talented live performer. A trained dancer, Applegate earned a Tony Award nomination in 2005 after taking on the title role in Broadway’s “Sweet Charity.” She has also impressed as a host on “Saturday Night Live.”

But that doesn’t mean she was happy with the show’s new creative direction—which can be seen as a desperate attempt to draw audiences.

There have also been a number of behind the scenes shakeups since showrunner Jon Pollack moved on. He was replaced twice. First by Tucker Cawley and later by Linda Wallem.

Emily Spivey, the show’s creator and executive producer, also recently left the series.

Applegate and Arnett have both had their share of failed TV shows.

Applegate’s 1998 sitcom “Jesse” was canceled after two seasons as was her 2007 series “Samantha Who.”

Arnett’s 2003 show “Arrested Development” was canceled in 2006 despite a small but deeply loyal audience, and has since become a cult phenomenon. His comedy “Running Wilde” premiered in 2010 but was canceled mid-season.

The actor will reprise his “Arrested Development” role for the show’s upcoming fourth season, which will debut exclusively on Netflix this spring.

Applegate is set to begin production on “Anchorman: The Legend Continues,” opposite Will Ferrell and Kristen Wiig, next month.