Manchester City hope to capitalise on Manchester United's Champions League distractions by re-launching the defence of their Premier League title, starting with Saturday's trip to Southampton.
City's 2-2 draw at home to Liverpool last weekend enabled United to stretch their advantage at the top of the table to nine points, with only 13 games of the season remaining.
However, while United will have half an eye on Wednesday's trip to Real Madrid when they host Everton on Sunday, City's own failure in the Champions League means their agenda is free of European commitments.
Aside from a home game against second-tier Leeds United in the FA Cup on February 17, City can therefore channel all their resources into the pursuit of United.
Ivory Coast's quarter-final exit at the Africa Cup of Nations means that City manager Roberto Mancini will have both Yaya and Kolo Toure at his disposal for Saturday's visit to the English south coast.
Yaya Toure played a key role in last season's drive to the title, when City came from eight points behind to pip United on the final day, and he says the experience of the 2011-12 campaign proves it is too early to abandon hope.
"We are further behind than we'd like, of course, but all we need to do is think about last season to know what is possible," the midfielder told the club's official website.
"Anything can happen. We have a full squad of fantastic players and I think the most important thing is we are all back together.
"United have a strong squad and on paper, they have an easier run-in than we do, but the title race is a long way from finished."
Everton's last visit to Old Trafford, in April last year, saw them come back from 4-2 down to force a 4-4 draw that played a pivotal role in tilting the momentum of the title race in City's favour.
As well as a two-legged tie with Madrid in the Champions League last 16, United are also scheduled to face Reading in the FA Cup, but manager Alex Ferguson is happy with the depth in his squad.
He told Inside United magazine: "We've got players back from injury, which is important, and I usually find that during the second half of the season when the big games come along, everyone is fit!"
The contest for third place took an intriguing turn last weekend, with Chelsea's 2-2 draw at Newcastle United enabling Tottenham Hotspur to close the gap on them to just a single point.
Spurs host improving Newcastle on Saturday lunchtime and with Chelsea playing at home to Wigan Athletic later that afternoon, victory for Tottenham will provisionally take them above their London rivals.
In another part of the capital, bottom club Queens Park Rangers are running out of time to close the six-point divide that currently separates them from safety.
Ahead of QPR's visit to League Cup finalists Swansea City on Saturday, new signing Christopher Samba says he saw encouraging signs in last weekend's 0-0 draw with Norwich City.
"I thought we did enough to win and we were unfortunate not to, as we could have had three points. That will come, hopefully against Swansea this Saturday," the former Blackburn Rovers centre-back told the QPR website.
"We played very well overall though, and I have seen we have enough to remain in this league for myself now."
With nearest rivals Wigan, Reading and Southampton all facing sides in the top half of the table, second-bottom Aston Villa could make up ground in the fight for survival by defeating West Ham United on Sunday.
Meanwhile, Jamie Carragher can expect an emotional reception when Liverpool welcome West Bromwich Albion to Anfield on Monday, having announced that he will retire from football at the end of the season.
Saturday (1500GMT unless otherwise stated):
Chelsea v Wigan Athletic, Norwich City v Fulham, Stoke City v Reading, Sunderland v Arsenal, Swansea City v Queens Park Rangers, Southampton v Manchester City (1730GMT), Tottenham Hotspur v Newcastle United (1245GMT)
Aston Villa v West Ham United (1330GMT), Manchester United v Everton (1600GMT)
Liverpool v West Bromwich Albion