With Premier League leaders Manchester United not playing until Sunday, champions Manchester City can close to within four points of their title rivals by beating Fulham on Saturday.
United have looked imperious in recent weeks, picking up 31 points from a possible 33 to establish a seven-point lead over second-place City, who have let 10 points slip over the same period.
However, on Sunday United visit Tottenham Hotspur, who have lost just once in 10 matches and who won 3-2 at Old Trafford when the sides last met in September.
With third-place Chelsea also preparing for a problematic assignment at home to Arsenal on the same day, City will hope this weekend marks the start of their fightback in the title race.
Whereas United and Chelsea were both in action in mid-week - United edging West Ham United in an FA Cup third-round replay and Chelsea drawing 2-2 at home to Southampton in the league - City have benefited from a week off.
Roberto Mancini's side have also been boosted by captain Vincent Kompany's successful appeal against the red card he was shown in last weekend's 2-0 win at Arsenal, which would have ruled him out of the home game with Fulham.
Although United show no sign of slowing, City full-back Pablo Zabaleta says his colleagues have not lost hope and will draw inspiration from the way they pipped Alex Ferguson's men to the English crown last season.
"We know that we are up against a rival in United who are in a very good moment," he said.
"They have seven points more, but that is not much in this league. There is still a long way before the title is decided and there is still a margin to lose and recover.
"We hope United have a few games where they lose some points and we continue on this route, taking three points all the time."
Further down the standings, Liverpool host Norwich City, knowing that victory, allied with a defeat for Spurs on Sunday, would take them to within six points of the Champions League places.
Brendan Rodgers' side went down 2-1 at United last weekend but there was good news in the return from injury of Italian striker Fabio Borini.
A close-season acquisition from Roma, Borini broke his foot just five league games into his Anfield career and after three months on the sidelines, he is desperate to make up for lost time.
"All the memories of the last three months and the things I've been through went from my mind," said the 21-year-old of his comeback at Old Trafford.
"My Liverpool career is actually starting now, I think. I'd only played five league games and six or seven games in the Europa League, which is not a lot.
"It really starts now with great intensity week in, week out to get playing again."
Saturday could also be an important day at the other end of the table, with the bottom five clubs all in action.
Newcastle United, two places above the relegation places, host second-bottom Reading, while Aston Villa will bid to arrest their worrying slide down the standings when they visit Midlands rivals West Bromwich Albion.
Fresh from their victory over West Brom in the FA Cup on Tuesday, bottom club Queens Park Rangers travel to manager Harry Redknapp's former club West Ham.
QPR will hope to hand a debut to French striker Loic Remy, who has revealed that a games console session with Malaysian chairman Tony Fernandes helped persuade him to join the London club from Marseille.
"It was a special moment that followed our chat about QPR," Remy told the club website.
"We just played a game of FIFA - it was good and showed to me what a good person Tony is. He showed his human side to me as an owner of the club I wanted to join. It was a special moment for us both."
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