Sadio Mane, Mohamed Salah, Edouard Mendy, Pierre-Emerick Aubameyang, Maxwel Cornet and more will be gone for several weeks
The Africa Cup of Nations begins next month, with about 40 Premier League players set to miss several weeks of the season as they head to Cameroon.
Watford have the most players eligible – six – although two are likely to miss out through injury.
Arsenal, Crystal Palace and Leicester are all set to wave four players off too, while Liverpool will lose three – including Mohamed Salah and Sadio Mane.
Chelsea are likely to be without keeper Edouard Mendy and Hakim Ziyech.
They could miss the Fifa Club World Cup and league games against Liverpool, Manchester City and Tottenham, among others.
Leeds, Newcastle, Norwich and Tottenham will not lose anybody.
As things stand, players could go after the games on 26 December, and those who reach the final may not be available again until Saturday, 12 February.
While the Africa Cup of Nations does not start until Sunday, 9 January, Fifa rules say clubs must release their players by Monday morning of the week preceding the week the tournament starts – which is 27 December.
Players can come back to England the day after their teams are knocked out, with the final and third-place play-off on Sunday, 6 February.
However, many clubs are currently negotiating with various national teams to try to delay the date they have to release their players.
The European Club Association (ECA) has expressed its "deep concerns" regarding player welfare before the tournament because of the "worsening public health situation" around Covid and is seeking urgent talks with world governing body Fifa.
No squads have been named yet but these are the players who could be gone.
Ismaila Sarr (Senegal)*, Peter Etebo*, Emmanuel Dennis, William Troost-Ekong (all Nigeria), Adam Masina, Imran Louza (both Morocco)
*Sarr and Etebo likely to miss out through injury
Thomas Partey (Ghana), Pierre-Emerick Aubameyang (Gabon), Nicolas Pepe (Ivory Coast), Mohamed Elneny (Egypt)
Crystal Palace (4)
Cheikhou Kouyate (Senegal), Jeffrey Schlupp, Jordan Ayew (both Ghana), Wilfried Zaha (Ivory Coast)
Leicester City (4)
Kelechi Iheanacho, Wilfred Ndidi (both Nigeria), Daniel Amartey (Ghana), Nampalys Mendy (Senegal)*
*Mendy is not in the Foxes' Premier League squad
Aston Villa (3)
Bertrand Traore (Burkina Faso), Trezeguet (Egypt), Marvelous Nakamba (Zimbabwe)
Frank Onyeka (Nigeria), Tariqe Fosu (Ghana), Julian Jeanvier (Guinea)
Naby Keita (Guinea), Mohamed Salah (Egypt), Sadio Mane (Senegal)
Edouard Mendy (Senegal), Hakim Ziyech (Morocco)
Alex Iwobi (Nigeria), Jean-Philippe Gbamin (Ivory Coast)
Manchester United (2)
Eric Bailly, Amad Diallo (both Ivory Coast)
Moussa Djenepo (Mali), Mohammed Salisu (Ghana)*
*Salisu is uncapped
Wolverhampton Wanderers (2)
Willy Boly (Ivory Coast)*, Romain Saiss (Morocco)
*Boly has not played in the Premier League because of injury this season but is expected to go to Afcon
Brighton & Hove Albion (1)
Yves Bissouma (Mali)
Maxwel Cornet (Ivory Coast)
Manchester City (1)
Riyad Mahrez (Algeria)
West Ham United (1)
Said Benrahma (Algeria)
Leeds United (0)
Newcastle United (0)
Norwich City (0)
Tottenham Hotspur (0)
What are some of the affected key games in this time?
- FA Cup third and fourth-round ties
- Chelsea's Fifa Club World Cup matches
- 28 December: Leicester v Liverpool
- 1 January: Arsenal v Manchester City
- 2 January: Chelsea v Liverpool
- 14 January: Brighton v Crystal Palace
- 15 January: Manchester City v Chelsea
- 16 January: Tottenham v Arsenal
- 23 January: Chelsea v Tottenham
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