Adrian Clarke looks at key tactical points and players who could be decisive in Matchweek 29.
Casemiro’s latest suspension is a severe blow to Manchester United, but Fred can step up to fill the void.
With few options in central midfield ahead of Sunday's match at Newcastle United, Erik ten Hag will be reliant on the 30-year-old.
Fred has impressed in flashes this season, despite failing to nail down a regular starting place.
In a match where he will be directly up against Brazilian compatriots Bruno Guimaraes and Joelinton, Fred will know that anything below his best could tip the balance in the home side’s favour.
Fred is a natural box-to-box midfielder, who consistently puts in maximum effort in every match.
Sometimes his technical ability can be found wanting, but nobody could question his desire to work hard for the team.
Compared to Man Utd’s other central midfielders, he runs further and presses more, with his 22.7 pressures per 90 minutes a considerably higher average than others in his position at the club.
The last time Fred started a Premier League away match without Casemiro by his side was in a 2-0 win at Leeds United in February.
He was excellent that day, especially out of possession.
When you check out his defensive chalkboard from that match, Fred’s natural inclination to cover the left-hand side is clear to see.
He covers for Luke Shaw very well and that could be useful at St James’ Park.
Anthony Gordon, if he is fit, will want to run at Man Utd's defence as often as possible, but moving across from the centre, Fred will do his best to crowd out his space.
Fred’s energetic all-action style also means he gets into advanced positions more often than other defensive midfielders.
If it is on him to break into the final third, he will not hesitate to join in with attacks, so Newcastle will need to track his runs.
He creates more chances and has more shots per 90 minutes than any other Man Utd central midfielder.
But without Casemiro, in a tough-looking away fixture, it is Fred’s off-the-ball work that may be his primary focus on Sunday.
Casemiro has received widespread praise for his displays this term, but statistically Fred outshines him for ball recoveries and successful tackles.
While Fred may be considered unfashionable by some, his importance to his team, especially on Sunday, will certainly be appreciated.
Part 2: Rice and Ward-Prowse duel key to vital clash at the bottom
Part 3: How lethal Alvarez can shine in absence of Haaland
Part 4: Stellini must plug the gaps in Spurs defence