A win could see them break into the top four spots, putting them in a great position with a game in hand on most other sides.
On the other hand, Man City will look to leapfrog Man United as both teams aim to close the gap on league leaders Tottenham Hotspur.
United were without strikers Anthony Martial and Edinson Cavani for their defeat at the hands of Leipzig and were forced to play a strike partnership of Marcus Rashford and Mason Greenwood. Solskjaer has confirmed that Martial will definitely be involved this weekend, however, despite returning to training, Cavani is still a doubt.
The Red Devils were also missing Fred on Tuesday night due to his Champions League suspension, but the Brazilian is available for domestic football and will make a return to the squad.
As for City, first-choice striker Sergio Aguero is not fit to start according to Pep Guardiola and although Ilkay Gundogan was withdrawn at half time against Marseille on Wednesday, it was thought to be purely precautionary.
United: De Gea, Wan-Bissaka, Lindelof, Maguire, Telles, Fred, McTominay, Greenwood, Fernandes, Rashford, Martial.
City: Ederson, Walker, Stones, Dias, Mendy, Rodri, Gundogan, Mahrez, De Bruyne, Sterling, Jesus.
Ones to watch
Bruno Fernandes has been in red-hot form this season having bagged seven goals and four assists in the league so far and picking up the Premier League Player of the Month award for November in the process.
The Portuguese playmaker was picked up an assist in this fixture last season as he set up Martial for the opener in United's 2-0 win and will be keen to influence the game again following the disappointment of crashing out of the Champions League.
On the blue side of Manchester, you would be a fool to look past Kevin De Bruyne when picking out a key player. Last season's PFA Player of the Year has managed two goals and six assists this season despite his injury issues.
The Belgium international will not want to be upstaged by his midfield rival Fernandes as they look set to face each other in a Manchester Derby for the first time.
Head to head
Solskjaer's men were victorious over their rivals in three out of the four times they played each other last campaign and currently sit above Guardiola's side by just one point in sixth place.
However, City knocked United out of the Carabao Cup in the semi-finals with an aggregate score of 3-2.
The Cityzens also enter this game with the better form in all competitions with four wins and a draw in their last five games compared to the Red Devils' three wins and two defeats.
Manchester United 2-1 Manchester City.
Where to watch on TV
The match will be shown live on Sky Sports with kick-off set for 5:30 PM.