The Reds do battle with their bitter rivals at Anfield after a thrilling Champions League win over Napoli, as they search for a first home victory over United since 2013.
Liverpool’s much-anticipated clash with United is one of 10 Premier League games to look forward over the next two days.
Here’s an overview of the rest of the action.
Man City vs. Everton – Saturday, 12.30pm – Sky Sports Main Event
A cynical view would be that this shows the lengths the Blues will go to ensure the Reds don’t win trophies, and they come up against the same opponents this weekend.
City’s 2-0 defeat at Chelsea last Saturday was a pleasant surprise, and Pep Guardiola’s side are actually under some pressure for the first time this season.
They remain a fantastic team, though, and while Marco Silva has turned Everton into a solid outfit in their own right, a home win seems highly likely.
Crystal Palace vs. Leicester – Saturday, 3pm
Perhaps it’s just bias because Liverpool fans have little time for him, but why isn’t Roy Hodgson under more pressure?
His Crystal Palace side are a lot more talented than their 16th-placed position suggests, with only one victory in their last 11 outings.
The Eagles host a good Leicester side on Saturday afternoon, but while the Foxes are superior, Palace could edge an ugly win sooner or later.
That may come this weekend, depending on which Leicester turn up, considering they have won and lost the same number of league matches (six) this season.
Prediction: Crystal Palace 2-1 Leicester
Huddersfield vs. Newcastle – Saturday, 3pm
This is set up as a relegation six-pointer, as Huddersfield welcome Newcastle to the John Smith’s Stadium.
Just three points separate the two teams and Rafa Benitez will be well aware of how priceless three points would be for the visitors.
Their last-gasp defeat at home to Wolves last Sunday was tough to take and they can’t quite pull away from the struggling pack.
Huddersfield remain in the bottom three—there is little to suggest that will change as the months pass.
Prediction: Huddersfield 1-1 Newcastle
Tottenham vs. Burnley – Saturday, 3pm
Two words: home banker.
Burnley are suffering a noticeable dip this season, despite picking up a typically gritty 1-0 victory over Brighton last time out.
Three more points will be added to Spurs’ total this weekend, strengthening their top-four hopes in the process.
Watford vs. Cardiff – Saturday, 3pm
His style of football may be grim, but the job Neil Warnock is doing at Cardiff is worthy of great praise.
After a tough start they have bounced back impressively, currently sitting 14th.
The Bluebirds head to Watford on Saturday with plenty of confidence, but the hosts should be too strong on the day.
Javi Gracia has built a team capable of finishing seventh, although no win since October is alarming.
They will stop the rot against Cardiff.
Prediction: Watford 2-1 Cardiff
Wolves vs. Bournemouth – Saturday, 3pm
Wolves’ aforementioned late victory at Newcastle was a massive bonus and they have recovered well from a dip in form.
They host Bournemouth on Saturday in a meeting between two teams who aim to play good football, so an entertaining encounter is on the cards.
Bournemouth offered little against Liverpool last Saturday, but they shouldn’t be judged too harshly, considering how imperious the Reds were.
Seventh place should still be the aim for Eddie Howe’s men—they are only three points behind sixth-placed United—and they will get something from Wolves.
Prediction: Wolves 1-1 Bournemouth
Fulham vs. West Ham – Saturday, 5.30pm – BT Sport 1
The only London derby of the weekend sees west take on east at Craven Cottage.
Fulham are propping up the rest of the Premier League and their 4-1 defeat at Old Trafford was worrying, considering how woeful Jose Mourinho’s team have been this season.
Their defence is alarmingly leaky, with 40 goals conceded in 16 games, and they will continue to struggle at the back against West Ham.
The Hammers are one of several clubs with European aspirations—finding a consistent level holds the key to that.
Prediction: Fulham 2-2 West Ham
Brighton vs. Chelsea – Sunday, 1.30pm
Chelsea gave Liverpool a massive helping hand by beating City—probably the only nice thing they have done to the Reds since Roman Abramovich bought the club.
It was a huge victory for themselves too, though, keeping their title hopes alive and ending a worrying run of iffy results.
They are strong favourites to overcome Brighton on Sunday, although anyone taking the Seagulls lightly is in for a rude awakening.
It won’t be plain sailing, but Chelsea will win.
Prediction: Brighton 1-2 Chelsea
Southampton vs. Arsenal – Sunday, 1.30pm – Sky Sports Main Event
Will Arsenal ever lose again?
Never has a team looked so beatable but put together such a strong run, even though it must be stressed that the Gunners have impressed hugely at times this season.
Unai Emery has instilled a winning mentality that Arsene Wenger failed to in the league late in his reign, and it is paying dividends.
They will fully expect to get the better of a Southampton side right in the relegation fight, but things should gradually improve with Ralph Hasenhuttl at the helm.