Clubs such as Arsenal and Newcastle United will be worst hit by the African Cup of Nations in January.
Out of Africa has some benefits for Premier League clubs
As Premier League players set off last week on international duty, their clubs will have been crossing their fingers they arrive back in one piece and not badly injured like England's Michael Owen after the 2006 World Cup.
Managers will have also been paying attention to matches in Africa and the final round of African Cup of Nations qualifying.
The surge, over the past 10 to 15 years, of talent from Africa into Europe has created a problem for the top clubs when their players leave for the Cup of Nations biennially for up to six weeks - at a time when title races are hotting up and the Uefa Champions League resumes.
Africa's biggest tournament is played in the cooler months of January and February. That makes it the only international competition to fall in the middle of the European club season and teams are obliged, by Fifa, to release their players.
You can understand the annoyance of Martin Jol, the then Tottenham Hotspur manager, when Freddy Kanoute chose to play for Mali instead of France in 2004. The striker had turned out for France's Under 21 team in 1998 and, when Spurs signed him from West Ham United, they presumed they were buying a player who would be available for the whole season.
Most Premier League clubs now have at least one African player. Chelsea, for example, will be without the Ivory Coast strikers Didier Drogba and Salomon Kalou when the 2012 African Nations Cup kicks off in Gabon and Equatorial Guinea. But they also have Daniel Sturridge, Fernando Torres, Romelu Lukaku and Nicolas Anelka as cover.
Manchester City, too, signed free agent Owen Hargreaves in preparation for Yaya Toure's absence in January.
Premier League clubs got a bonus this week with the news that several of Africa's heavyweight nations - Nigeria, Cameroon and South Africa - failed to qualify for the tournament.
Chelsea can now count on John Obi Mikel, the Nigeria midfielder. Tottenham Hotspur will have left-back Benoit Assou-Ekotto and West Bromwich Albion won't lose Peter Odemwingie, their top scorer last season.
The biggest losers? Newcastle United will miss Demba Ba and Chiek Tiote. Queens Park Rangers will have to do without their influential winger, Adel Taarabt.
But Arsenal could be worst hit. Gervinho and Marouane Chamakh will play for their countries, meaning Arsenal will have just two out-and-out strikers.
And, given Robin van Persie's injury record over the last few years, it is not inconceivable that Park Chu-young, the South Korea captain, could be left carrying the can up front at a time when, last season, Arsenal fell out of title contention.