The midfielder is set to miss three months after picking up a knee injury in the draw with Norwich.
The Spanish midfielder picked up a knee ligament injury during the Premier League game with Norwich City at Carrow Road on Sunday.
He was, however, forced to play on in the game after the Gunners had used all of their substitutions, with stars Alexis Sanchez and Laurent Koscielny having also picked up knocks.
Arsene Wenger did fear the worst after the game, and now those fears have come true, with it looking like he is set to lose his star man for an extended period of time.
The midfielder has been a key part of the Gunners midfield this season, forming a solid partnership with Francis Coquelin once again.
And following the announcement of the news, Arsenal fans took to Twitter to reveal their thoughts, with most of them none too pleased:
Santi Cazorla out for three months, that's devastating for Arsenal's season— Stuart Hynd (@supers0nic_) December 2, 2015
Can @arsenal please go into liquidation? Cazorla Sanchez Coquelin Koscienly Wilshere Walcott Welbeck Gibbs injured. FFS ,this is ridiculous!— Mike (@itsmikehyl) December 2, 2015
So we are without our first-choice midfield of Coquelin & Cazorla for 3 months. The footballing gods have got it in for Arsenal— GunnerPride (@Gunner_pride) December 2, 2015
The Cazorla injury estimated at "at least" 3 months is the most Arsenal thing I can think of. "At least."— Dan Ahern (@topical_storm) December 2, 2015
Absolute awful news that Cazorla is not back until March! The reason Arsenal haven't won the PL for years is not down to Wenger but Injuries— ĎĆ11 (@Ozlexis) December 2, 2015
Cazorla out for 3 months - The annual Christmas collapse has begun for Arsenal.— James Guihen (@James_Guihen) December 2, 2015