With second-place Arsenal not in Premier League action this weekend, Manchester United can increase its lead at the top of the standings with wins at Wigan and fading rival Chelsea in a four-day span.
United's cushion is down to one point following Arsenal's 1-0 victory over Stoke on Wednesday, but the Gunners face a 10-day break from league play, allowing their northwest rivals an opportunity to take advantage.
Faced with the prospect of going seven points clear, United must beat a Wigan team battling to avoid relegation before turning its attention to Chelsea, whose focus now is qualifying for next season's Champions League rather than defending its title.
Arsenal will look to end its six-year trophy drought when it plays Birmingham in the League Cup final on Sunday, but will have one eye on developments in the Premier League title race.
The Gunners, who have played one game more than United, need Alex Ferguson's side to start slipping - so far, it has lost just once in the league.
"We have some massive games coming up," United winger Nani said. "The next few weeks are going to be very important for us.
"We are focused on winning every game because we know the results in the next few matches could prove decisive."
Wigan is third from bottom in the standings, but is unbeaten in its last three league games and halted Liverpool's upward surge with a 1-1 draw at Anfield in its last match.
"We will go into the game believing we can be better than them on the day," said Wigan left back Manuel Figueroa ahead of Saturday's game.
"After the last three league games, our confidence is high and instead of worrying ourselves with league positions, we're focusing instead on our own performances, which been the key."
Chelsea manager Carlo Ancelotti all but conceded the title after his team's 0-0 draw at Fulham last week but a victory over United on Tuesday, which would leave the Blues nine points off the lead, could alter his view.
"If we want to put in a charge for the Premier League then we must beat Manchester United," Chelsea captain John Terry said. "A draw is no good and obviously losing is no good at all.
"We will go into the game with no fear, plenty of passion and being able to put pressure on them will be great. We have been there, we have seen it, done it and we have got the T-shirt. We have got a lot of experience and trust in one another and belief that we can still do it. That's a testament to ourselves."
Manchester City is eight points adrift of its cross-town rival after losing the Manchester derby 2-1 on Feb. 12 and, like Chelsea, will now be concerned about preserving its place in the top four.
On Sunday, City hosts Fulham, whose run of one defeat in seven league matches has lifted the team four points clear of the relegation zone. The London club also has a superb record at the City of Manchester Stadium, having lost just once since City moved there in 2003.
Fourth-place Tottenham has the weekend off, so resurgent Liverpool can move five points behind Harry Redknapp's side by beating second-bottom West Ham in Sunday's other match.
There are four other matches on Saturday, with last-place Wolverhampton Wanderers hosting Blackpool, fifth-bottom Aston Villa at home to Blackburn, Sunderland at Everton and Bolton traveling to Newcastle.
Stoke hosts fourth-bottom West Bromwich Albion in Monday's match.
Arsenal could be without a number of important players for the trip to Wembley.
England winger Theo Walcott is out with a sprained ankle while captain Cesc Fabregas (hamstring), striker Robin van Persie (hamstring) and defender Laurent Koscielny (back) are all doubts.
Fabregas was forced off after 14 minutes of the win against Stoke but said he would try his hardest to prove his fitness.
"I don't know if I'll make Sunday or not, but all I know is that from this moment to Sunday I won't sleep if it's necessary," the Spain midfielder posted on his Twitter account. "I've waited too long to captain a final for Arsenal and I won't give up till the last second."
The Gunners' last trophy came in 2005, when they beat Manchester United on penalties to win the FA Cup.
The 1963 League Cup is the only piece of major silverware in Birmingham's history.