The tournament was delayed due to the coronavirus pandemic and wet weather concerns, but is now set to start this weekend with a host of big-name players jetting off to the continent.
The 2021 AFCON was initially due to be held in June and July 2021, but has been put back to early 2022.
It will now take place from January 9 to February 6 2022, with Cameroon the host nation.
The timing of the competition's move will undoubtedly lead to frustration from Premier League managers, who will be presented with a big challenge to cope without their star men, with some set to be gone for almost a month of action.
None more so than Liverpool and Arsenal who arguably have the toughest jobs on their hands.
Mohamed Salah, Sadio Mane and Naby Keita will all leave the Reds for Egypt, Senegal and Guinea respectively.
Meanwhile, Gunners stars Pierre Emerick Aubameyang, Nicolas Pepe and Thomas Partey will join up with the Gabon, Ivory Coast and Ghana squads.
Man City will also be without Riyad Mahrez of Algeria, the current holders from the last edition in Egypt 2019 who will be aiming to retain their title.
But those Premier League giants will not be the only clubs that will be left short during the crunch New Year period.
Here's a list of all the top-flight players set to take part in the AFCON and miss Premier League action in early 2022: