Liverpool will be determined to bounce back from FA Cup embarrassment when they take on Arsenal, while leaders Manchester United entertain Southampton.
There are points to play for in the race for European qualification and the battle against relegation as Chelsea visit Reading, Tottenham Hotspur travel to Norwich City and Everton entertain West Bromwich Albion, while Fulham face London rivals West Ham United.
Arsenal and Liverpool may not be competing for the title this season but there is still an intense rivalry between the sides and Wednesday's meeting at Emirates Stadium promises to be a thriller as the fight for UEFA Champions League football intensifies. Brendan Rodgers was critical of his side's performance after they lost to Oldham Athletic in the FA Cup on Sunday and will be demanding an improvement against the sixth-placed Gunners, who had to work hard themselves to see off Brighton & Hove Albion.
Mauricio Pochettino made a steady start to his Southampton reign following the controversial sacking of Nigel Adkins with a goalless draw at home to Everton but an even sterner test awaits at Old Trafford in midweek. Manchester United conceded a last-gasp equaliser to Spurs in their most recent Premier League outing and will be focused on returning to winning ways, having seen Manchester City squander the chance to cut their lead at the summit to two points as they drew 0-0 with bottom club Queens Park Rangers on Tuesday night.
Third-placed Chelsea journey to the Madejski Stadium to take on a Reading side still in the relegation zone despite an encouraging run of form. The Royals have staged superb comebacks to beat West Brom and Newcastle in their past two games, while they thrashed Sheffield United in the FA Cup. Chelsea survived a cup scare as they twice came from behind to earn a replay against Brentford but Rafa Benitez's position as interim manager has once again come under the microscope.
Norwich meet Tottenham at Carrow Road in a clash between two teams to fall victim to FA Cup shocks at the weekend. Chris Hughton's Canaries became the first Premier League side in 24 years to get knocked out by a non-league club as they were defeated by Luton Town, while Leeds United proved too good for Spurs at Elland Road. Tottenham have at least been in fine form in the league and are currently fourth following a seven-match unbeaten run, whereas Norwich have plummeted down the standings after failing to win in six.
If Spurs do slip up, then Everton will be looking to capitalise when they welcome West Brom to Goodison Park. David Moyes' men are three points adrift of fourth spot after being held to goalless stalemates in their past two league encounters but face a tough challenge against a Baggies side still in contention for Europe despite a run of four games without a win.
Two points separate capital rivals Fulham and West Ham ahead of their game at Craven Cottage. Fulham are the side closest to the drop zone and both will be wary of getting sucked into a scrap for survival. The Cottagers have won just twice in 15 games since making a strong start to the season, while consistency has proved similarly elusive for the Hammers as they have just one victory in their last eight.
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