Cristiano Ronaldo will miss Sunday's Manchester derby due to a hip injury.
With Edinson Cavani also absent from the matchday squad and Marcus Rashford on the bench, United's attack does not feature an out-and-out striker, with Bruno Fernandes, Jadon Sancho, Anthony Elanga and Paul Pogba set to operate in forward areas at the Etihad Stadium.
Manchester City will have a similarly fluid front line, with Phil Foden, Jack Grealish, Riyad Mahrez and Bernardo Silva in the hosts' attack, but they are missing injured centre-back Ruben Dias, in a game you can watch live on Sky Sports Premier League from 4pm; kick-off 4.30pm.
This will be just the second Premier League game 37-year-old Ronaldo has missed since rejoining United this season, however, he has scored just one goal in his last 10 appearances.
Speaking ahead of kick-off on Super Sunday, Sky Sports pundit Gary Neville said Ronaldo's forced absence may not be as big a blow as it may seem, given the style of play United are likely to employ against their neighbours - although he had expected Rashford to start up front in Ronaldo's place.
"United over the last three or four years were a counter-attack team, really comfortable sitting back punching out on the break and that will be exactly the same today," he said.
"Cristiano not being in the team, I could never say it's a positive, but I don't see it as a big loss that I might do in other games."
Former striker Andy Cole - who played up front for both United and City - believes Pep Guardiola's defenders will be pleased by the news Ronaldo is not playing.
"You can talk about his age and what people perceive him to be contributing in games but if he's not playing, as a centre-half, I'd be a lot happier," Cole told Sky Sports News.
"You know if he gets half a chance there's a good chance he'll take it. You don't get as many goals as he has throughout his career if you don't know what you're doing when you get in the box."
However, Sky Sports' Paul Merson had said on Soccer Saturday he believed the visitors would have a better chance of winning at the Etihad Stadium if Ronaldo was dropped.
"I'd play [Marcus] Rashford and [Anthony] Elanga," said Merson. "If they've got any chance of winning this game, they have to play on the counter-attack with plenty of pace, skill and energy.
"Personally, I'd leave Ronaldo out of this game. Against Watford, they dominated the game and had something like 80 per cent possession, but they're not going to have the ball as much against City.
"How many times are they going to be in City's half dominating the ball? If you're John Stones or Aymeric Laporte, they would rather play against Ronaldo than mark someone like Rashford. They don't want to play up against pace."