Premier League managers have grumbled about the timing of Africa's biennial championship for years, complaining about the fact that the tournament deprives them of players just when the fixture list is at its busiest.
But the 2012 tournament, which kicks off in Gabon and Equatorial Guinea on Saturday, could have an even bigger impact in England than normal as clubs such as Manchester City, Chelsea and Newcastle grapple with several absentees.
Nowhere is the Cup of Nations more unpopular than at Eastlands, where City manager Roberto Mancini is glumly resigned to the loss of Ivorian brothers Yaya Toure and Kolo Toure when his team can least afford it.
In many respects the loss of the Toure duo has already been felt by City, who have led the league for much of the season.
Since the players departed to link up with the Ivory Coast squad earlier this month, City have lost key games against Manchester United in the FA Cup and Liverpool in the semi-final of the League Cup.
More pertinently, City were comfortable 3-0 winners over Liverpool in the League on January 3, with Yaya Toure influential throughout, before losing 1-0 in the League Cup a week later when the midfielder was missing.
"I have tried to find another Yaya in my squad but there isn't another Yaya," said Mancini recently.
"He is a very important player. For this reason January is a big month. If we can stay on the top of the table after January then I think we have a very good chance to win the league."
City's nearest challengers in the title race, Manchester United and Tottenham, will not be affected by the Nations Cup.
None of the Africans in Spurs squad, including Togo striker Emmanuel Adebayor, represent Nations Cup qualifiers, while the lone African on United's books, Mame Biram Diouf, has been overlooked by Senegal.
Yet while Spurs and United are primed to pounce on any slip-ups from City, other sides near the top of the table have not been so fortunate.
Chelsea manager Andre Villas-Boas will be hoping that Spanish striker Fernando Torres finds his goalscoring boots sooner rather than later as the club bids farewell to Didier Drogba and Salomon Kalou.
Drogba, who is at loggerheads with Chelsea over his future, has been the club's best striker this season and his absence will become even more acute should Torres fail to rediscover his best form.
Chelsea's challengers in the race for a top four finish, Arsenal, could also suffer from the absence of the Ivory Coast's Gervinho and, to a lesser extent, Moroccan international Marouane Chamakh.
Chamakh has remained a peripheral figure at the Emirates this season but Gervinho has been a key source of assists during Robin van Persie's scoring run.
Arsenal manager Arsene Wenger believes the impact of the Nations Cup will be felt for several weeks after its conclusion.
"It is the equivalent of a player here going to the European Championship. They are under immense pressure," Wenger said.
"It is a different climate (over there). Usually we have snow in February here, so they come from a big temperature difference. Most of the time, they are dead (afterwards)."
Newcastle manager Alan Pardew meanwhile is hoping his team can maintain their impressive start to the season --- which has seen the Magpies climb to sixth place -- in the absence of star striker Demba Ba and midfielder Cheick Tiote.
Senegal forward Ba netted his 15th goal of the season in the 3-0 victory over Manchester United earlier this month, a game in which Tiote dominated in midfield.
Pardew has vowed to fly out to the Nations Cup if either of his players are involved in the final.
"The one thing I will do is that if either is in the final Ill be going out to make sure they come home," he said.
"They wont be partying for a week after or anything -- theyll definitely see me in the stand if they get to the final.
"The most important thing is they come back fit. Coming back fit and well is all I care about."
Africa Nations Cup absentees could also be influential at the other end of the table, with Wigan losing Mohamed Diame as they try to claw their way out of the relegation quagmire along with Queens Park Rangers, who will be without Moroccan playmaker Adel Taarabt and Senegalese defender Armand Traore.