With the majority of the squad having a rest during the international break, head coach Steve Bruce has a few new options to choose from.
Ciaran Clark, Paul Dummet, and Jamal Lascelles have all been back into training, which gives Bruce plenty of defensive choices to pick from.
Only three players are still on the injury list for Newcastle this weekend Matt Ritchie, Dwight Gayle and Martin Dubravka.
Bruce will hope that his side's 3-1 victory against Burnley can translate across the break. A win against Man U would undoubtedly calm the critics of Bruce.
Here is VAVEL's predicted Newcastle starting XI.
Goalkeeper - Karl Darlow
The Englishman tops the league in saves this season with 20. His impressive season will get a chance to continue as a complication has occurred in number one Dubravka's heal injury which has ruled him out until December.
This will be Darlow’s longest stint between the sticks for The Magpies since 2018. Long may his excellent form continue.
Right Back - Javier Manquillo
Since the project restart, Manquillo has been the best right-back at Newcastle.
Emil Krath has improved with each coming game in the position. However, with Man United's suspect full-backs, Manquillo's attacking threat cannot be overlooked. The Spaniard is in the top ten of all Premier League full-backs of crosses completed, which is not a stat be ashamed of.
Centre-Back - Jamaal Lascelles
The Captian has used the international break to regain his fitness. Lascelles form has been excellent this season, so he becomes one of the many players in this talented squad in the position of if he is fit he plays.
Newcastle has had other options come back in the international break with Fabian Schar playing both times for Switzerland he could feature in the Englishman's place if Bruce doesn't think he is fit enough.
Centre-Back - Federico Fernandez
The Argentian has continued last seasons high-quality play, he has been The Magpies rock at the back this season.
With Fernandez being second in clearances in the entire Premier League with 21, he is a sure-fire starter for this team.
Left Back - Jamal Lewis
With more time to heal following the eye injury, Lewis will start for Newcastle against Man U.
His Partnership with Allan Saint-Maximan is going to be a plus on his resume. The former Norwich City man has been brilliant since his move to the North-east. His defensive capabilities will most certainly be tested against either Marcus Rashford or Mason Greenwood but Lewis is talented and more than capable.
Centre Midfield - Issac Hayden
Hayden is Newcastles utility man this season, featuring at centre back as well as his defensive midfield role.
Hayden leads the club in tackles, interceptions and touches this proves how vital he is to the side. Since Bruce's appointment back in 2019 Hayden has been a prominent player for The Magpies his play has gone from strength to strength. It will have to continue on Saturday to contain the £120 million midfield Man U have.
Centre Midfield - Jonjo Shelvey
Shelvey has been crucial to The Toon Armies counterattacking style this season with his pass completion hitting a two season-high of 73% pass accuracy.
His partnership with Hayden is vital as it allows Shelvey to push forward and join in the attack, this is shown by the Englishman completing the second most crosses for The Toon, a sure starter for Saturday.
Right Midfield - Allan Saint-Maximin
Six more years. The sound of that should bring a smile to every Newcastle fan. The Frenchman has joined so many of his compariates in our hearts. Names who are legendandry from both the past and present, David Ginola, Lauren Robert, Hatem Ben Arfa. ASM is a player who if he is fit he plays. He is fit, he will start.
Centre Attacking Midfield - Joelinton
The Magpies number nine has seen a turn of form, with his new role running off the central striker. Joelinton has been able to be involved in the build-up and will have a much better year. The physicality will be crucial against a big and strong Man U backline, but the pace will be even more necessary.
The other factor is Miguel Almiron played in South America so his travel distance will most likely leave him on the bench.
Left Midfield - Ryan Fraser
Fraser was one Newcastle's international call ups. He rewarded Steve Clarke's belief in him with his first goal for Scotland.
Fraser is arriving at full fitness and with that the Scot has a point to prove to his critics, belive he shouldn't have missed eight months of football and helped Bournemouth at the end of last season. Fraser didn't he is at Newcastle for a fresh start.
He'll get it here, a fresh start against Man U.
Central Striker - Callum Wilson
Four goals, four games, one assist, 83 per cent goal contribution to The Magpies total goals this season. It has been a little while since Newcastle fans can look at a striker and go we can have 15 goals minimum from you. This is what Wilson brings. Start him, and goals come. Goals win you football games. In essence, Wilson will start.