Premier League braces for the much anticipated Manchester derby as United makes a short trip to league leader City on Sunday.
Elsewhere, a struggling Leeds United will begin life under new boss Jesse Marsch, while Liverpool will seek to make it seven league wins in seven against high-flying West Ham, one of only two sides to beat the Reds this season.
Arsenal could take advantage of visits to the top two for the Hammers and United by moving into fourth with games in hand to come when it travels to Watford.
As City's crosstown rival comes for a visit, Pep Guardiola's side will look to end its United-Etihad jinx. Even though City is now indisputably the top dog in Manchester, it has had real problems beating United on its own turf in recent years.
The Premier League champion has won just one of its past seven home games in all competitions against United – in sharp contrast to its impressive record at Old Trafford.
Both teams need the three points Sunday, with leaders City seeking to keep Jurgen Klopp's charging Liverpool at arm's length and United's top-four hopes looking shaky.
The fourth-placed Reds are just two points ahead of West Ham and Arsenal as they seek to secure Champions League qualification for next season, while the Gunners have three games in hand.
City, who tends to dominate possession, has been caught out in recent years by United's pace on the break and Pep Guardiola will be wary of the threat posed by players such as Jadon Sancho and Marcus Rashford.
United has lost just one league game since interim manager Ralf Rangnick took charge in December but this is by far his toughest task yet.
New Leeds boss Jesse Marsch has two huge tasks – following in the footsteps of the hugely popular Marcelo Bielsa and tightening up a horrifically leaky defense.
Leeds has conceded an eye-watering 60 goals in the Premier League this season – five more than any other team.
It is just two points and two places above the relegation zone after four straight defeats under the sacked Argentine.
Leeds, who travels to Leicester on Saturday, conceded 20 goals in February alone in the Premier League – the most a side has ever shipped in a single month in the competition.
The American former RB Salzburg and RB Leipzig boss has expressed his "massive" admiration for Bielsa as he begins the task of saving the club from relegation.
"Everything that's been done has laid an incredible foundation and coming into this moment I just want to try to do everything I can to help take the club into the next phase of our history," he said.
Arsenal, for so long a fixture in the Champions League under Arsene Wenger, has a golden chance to return to Europe's top club competition after five seasons away.
Mikel Arteta's side is the favorite to seize the fourth spot, which secures entry into the competition, after recovering strongly from a disastrous start to the season.
The Gunners slumped to the bottom of the Premier League table after losing their first three matches but have stormed up the table since.
Arsenal, who face relegation-threatened Watford on Sunday, will overtake United if it makes the most of its games in hand.
Its three recent wins on the bounce have come despite a lack of resources up front following the departure of forward Pierre-Emerick Aubameyang to Barcelona.
Speaking about the importance of qualifying for the Champions League, Arteta said: "This has to be the aim every year to be playing among the best teams in the world and that's what we want to do."
Leicester vs. Leeds
Aston Villa vs. Southampton
Burnley vs. Chelsea
Newcastle vs. Brighton
Norwich vs. Brentford
Wolves vs. Crystal Palace
Liverpool vs. West Ham
Watford vs. Arsenal
Manchester City vs. Manchester United
Tottenham vs. Everton
