Premier League champions Manchester City travel to north London to face Arsenal in the second part of a high-profile double-header; league leaders Manchester United kick off earlier in the day and host Liverpool at Old Trafford.
With only seven points separating the two Manchester clubs at the top of the table, the struggling Reds and Gunners will have their work cut out if they want to take points off two of England's best footballing outfits.
There are the European champions and Tottenham to consider as well. Chelsea and Andre Villas-Boas' Spurs are only four and five points behind City in the race for second and should Roberto Mancini's men slip up at the Emirates, the champions will not only see United potentially disappear into the distance but also find themselves dropping back within reach of the Blues, Tottenham and even Everton in fifth.
The season's reverse fixture ended in a 1-1 draw, with French international Laurent Koscielny earning the Gunners a deserved point at the Etihad.
Where to Watch Live
Kick-off is set for 4pm GMT. Live coverage is available on Sky Sports 1 and Sky Sports 1 HD, with radio commentary on BBC Radio 5 live. Catch the highlights on BBC One and BBC One HD's Match of the Day 2, which starts at 10.25pm GMT.
Arsenal should be hosting City with the knowledge they have progressed to the fourth round of the FA Cup. Unfortunately for the Gunners, the third round tie, against Swansea City, will have to be replayed after Danny Graham scored in the 87th minute to leave the scores level at 2-2.
The Gunners looked to have the match sewn up after goals in the 81st and 83rd minutes from Lukas Podolski and Kieran Gibbs gave Arsene Wegner a 2-1 lead. In-form Spaniard Michu had given the Swans the lead just before the hour mark. However, Graham's last-gasp goal will mean the Swansea-Arsenal battle of wits will be played out once more this season.
The match was perhaps symptomatic of Arsene Wenger's run of form in recent weeks. The north London club looked to have entered a wonderful run of form, at just the right time in the season, when they won three times in succession in late December. Wins against Reading, Wigan and Newcastle (the last a mammoth 7-3) looked to have erased memories of the penalties defeat to Bradford City in a Capital One Cup fixture.
However, since then the club has drawn twice in succession and both were games they should have won; the first was a lacklustre 1-1 draw St Mary's in the Premier League and the second was the Swansea match.
The good news though is that the Gunners are unbeaten, in regulation time, since the early December Champions League group stage loss to Greek side Olympiakos; and that match was a dead rubber.
The Emirates continues to be a difficult place for visiting teams, with the home side having lost only twice in ten games this season. The record of 13 goals conceded is not ideal, considering City, Chelsea, Spurs and at least five other sides have better defensive records at home. However, Arsenal fans should be reasonably confident of scoring goals as well, with only league leaders United having scored more (28) than Arsenal's 25 in home fixtures.
City, meanwhile, are a compact if unexciting away side. The champions have lost just once in 10 games on the road, which is the best record in the league. The problem is that they've drawn four of the remaining nine.
Mancini's men have recently rediscovered their goal-scoring form, though, which will concern Wenger. City have scored at least three goals a game for three games in succession and have kept two clean sheets in a row. The swagger that was so evident for large parts of last season appears to be returning, even if there are a number of rumours linking key players with moves away from the Etihad.
The club's last game was a solid 3-0 home win over Watford in the third round of the FA Cup, with Tevez putting in an excellent shift. Rather surprisingly, the striker who caused so much trouble last season is Mancini's go-to man at the moment and has an impressive seven goals and five assists from 15 Premier League starts.
- Last Five (all competitions, most recent first): D D W W W
- Last Match: Swansea City 2 - 2 Arsenal
- Last Five (all competitions, most recent first): W W W L W
- Last Match: Manchester City 3 - 0 Watford
Wenger will sweat on the fitness of Olivier Giroud (knee); the French striker faces a late fitness test. His compatriot, the oft-injured midfielder Abou Diaby, played an hour for the club's reserve team in a midweek game but still requires match fitness and given the importance of the game and the quality of the opponents, he is unlikely to be risked.
Polish goalkeeper Lukasz Fabianski (ankle) is still unavailable, as is Brazil left Andre Santos. Ivory Coast international Gervinho is away with his national side for the 2013 African Cup of Nations.
Probable Line-Up: Szczesny; Sagna, Mertesacker, Vermaelen, Gibbs; Arteta, Wilshere; Oxlade-Chamberlain, Cazorla, Podolski; Walcott
Meanwhile, City travel to London without their most important player. Ivorian midfielder Yaya Toure has left the club to join up with his national squad for the African Cup of Nations, leaving a considerable hole in the champions' midfield. The former Barcelona star has been joined by his brother, ex-Arsenal defender, Kolo Toure.
The problems pile up for Mancini with the absence through injury of Argentine striker Sergio Aguero; the ex-Atletico Madrid man has a hamstring problem. A second ex-Arsenal player, French midfielder Samir Nasri, is unavailable because of disciplinary issues.
The list of injuries also includes Serbian left back Aleksandr Kolarov (groin), England midfielder Jack Rodwell (hamstring) and right backs Maicon and Micah Richards (both knee).
Probable Line-Up: Hart; Zabaleta, Kompany, Nastasic, Clichy; Javi Garcia, Barry; Silva, Tevez, Milner; Dzeko