Michael Carrick's men are 13th in the Premier League and could even drop into the bottom three if results go against them this weekend.
At the other end of the table, Manchester City aim to extend their flawless start to the season at Aston Villa, despite doubts over the club's future in the English top-flight.
Third-placed Brighton are dreaming of an unlikely title challenge but face a stiff examination when they travel to Liverpool.
AFP Sport looks at the pick of the Premier League action this weekend:
Man Utd back in crisis mode
The Red Devils sank to new depths during a terrible start to the season in a 4-1 thrashing by Champions League debutants Como in midweek.
Captain Bruno Fernandes took aim at his manager's passive tactics after the match, saying United had to be more "brave".
But Carrick, who apologised to the travelling fans in Italy, hit back at his players for not covering enough ground.
"Whatever system you play, whatever tactics you play, if you don't run and you don't run forward, and you don't run back, you ain't going to win," said the former United midfielder.
The blunt remarks come just a week after defender Lisandro Martinez criticised the club's board for not investing enough in the transfer market.
United's return of seven points from their opening seven games is their lowest of the Premier League era.
After the departures of Erik ten Hag and Ruben Amorim in the past two seasons, United are facing another campaign of transition unless Carrick can quickly right the ship.
Brighton hungry for more
Only Barcelona have outscored Brighton in Europe's top five leagues this season, with the Seagulls netting 23 times in their seven games.
Brighton have soared through the divisions and into Europe on the back of owner Tony Bloom's expertise in data analytics, but they are yet to win a major trophy in their 125-year history.
Matching Leicester's remarkable title triumph a decade ago still seems unlikely, but Brighton will get a clearer idea of where they stand after visits to Anfield and Manchester City in the next two weekends.
Despite routinely selling their prized assets to wealthier clubs, Brighton's smart recruitment of both players and coaches has ensured they have continued to thrive.
"We can enjoy it, but on the other side it's also very important to stay humble and stay grounded because in football things can change quickly," said 33-year-old manager Fabian Hurzeler.
"We have to have this hunger inside of us to keep going and never be satisfied - to keep pushing."
City face Villa Park demons
Manchester City boss Enzo Maresca is the first manager to win his first seven Premier League games in charge of a new club.
Yet it may all count for nothing unless City are successful in their appeal after being found guilty of more than 100 breaches of Premier League financial rules.
Maresca's men travel to Aston Villa on Saturday, hoping to improve on a miserable recent record in Birmingham.
City have lost on their past three visits to Villa Park and face a resurgent opponent after an overhaul of Unai Emery's squad in the transfer market.
Villa have won five and drawn one of their past six games in all competitions as new signings Nicolas Jackson, Johan Manzambi and Zion Suzuki have quickly settled in to mitigate the loss of Ollie Watkins, Morgan Rogers and Emi Martinez.
"How we are responding, getting better, is really fantastic," Emery said after Villa beat Viking to make it three wins from three in the Champions League.
"How some individual players are feeling comfortable and getting confidence and getting better rhythm on the field is really as well something (that) makes us happy and confident (in) ourselves."