This weekend will see the squad strength of several Premier League clubs put to the test as they face up to life without players now required by their respective countries for the African Nations Cup.
Table-toppers Arsenal, two points clear of champions Manchester United, go into their home game against Birmingham City without Kolo Toure, Emmanuel Eboue and Alexander Song, all on their way to the Nations Cup in Ghana.
As if that were not bad enough for the Gunners, defenders Philippe Senderos and Johan Djorou are both injured.
Gilberto Silva is likely to line-up alongside William Gallas at the back.
But unlike several managers in English soccer's top-flight who can be heard complaining about the timing of the three week Nations Cup, Arsenal's French boss Arsene Wenger is willing to accept the consequences of signing those players who are eligible for the tournament.
"I won't use [the African absentees] as an excuse if we don't win the title because I've known who we will lose since the start of the season," he said.
The build-up to Manchester United's meeting with Newcastle United has been overshadowed by the departure from St James' Park of manager Sam Allardyce.
But given a run that has seen Newcastle take just nine points from 12 games and last weekend's uninspired goalless draw against Championship side Stoke City, Allardyce was always likely to be on thin ice particularly as the team were not playing the flowing soccer beloved of so many Newcastle fans.
Allardyce's tenure with the Tyneside club lasted a matter of months but by contrast, Sir Alex Ferguson is now entering his 22nd year in charge.
Today's match at Old Trafford could see Ferguson able to field his first-choice forward pairing of Wayne Rooney and Carlos Tevez after injuries to the duo.
"We have a strong season ahead of us, so it is important Wayne is ready along with all the other players as well," United's Cristiano Ronaldo said.
Chelsea too have been depleted by the call of Africa.
Ivory Coast internationals Didier Drogba and Salomon Kalou, Nigeria star John Obi Mikel and Ghana's Michael Essien are all away for the biennial competition.
Meanwhile injuries to goalkeeper Petr Cech, defender and captain John Terry, midfielder Frank Lampard and striker Andriy Shevchenko have created problems even for a club of Chelsea's resources.
One consolation for Blues manager Avram Grant ahead of today's home match against Tottenham Hotspur is that Chelsea's London rivals have not won in the league at Stamford Bridge for close on 18 years.
Everton and Manchester City, two teams on the verge of breaking into England's elite, go head-to-head at Goodison Park, basement club Derby County are at home to fellow drop candidates Wigan Athletic in what could be Robbie Savage's first match for the Rams since he joined earlier this week.
Liverpool, currently outside their customary place in the leading quartet, travel to Middlesbrough, while second-bottom Fulham will look to kick-start their push for Premier League survival in a London derby with West Ham United.
Tomorrow, Sunderland -- also relegation candidates -- are at Fratton Park where the hosts Portsmouth have not scored in the league since September.
Sunderland manager Roy Keane said that if his side were to improve on a run of just two wins in 16 matches in all competitions it was vital his players improved their discipline.
"Some of our yellow cards and our sendings-off, I really think we have no-one to blame but ourselves," said Keane, himself not always on the right side of referees during his time as a Manchester United midfielder.
Pompey are currently eighth in the table but have four players -- strikers John Utaka and Kanu and midfielders Sulley Muntari and Papa Bouba Diop -- at the African Nations.
But that does give a chance to striker David Nugent, who scored the south coast side's winner against Ipswich Town in the FA Cup last weekend, to make his manager regret not signing him when he had the chance to during the pre-season.
Blackburn Rovers will have South Africa international striker Benni McCarthy available for their match with Bolton Wanderers.
McCarthy scored 24 goals in all competitions for Rovers last season.
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