Both familiar to boss Erik ten Hag from their time together at Ajax, Matthijs de Ligt and Noussair Mazraoui recently arrived from Bayern Munich, just in time to add numbers to an injury-hit defensive department.
Not only is new signing Leny Yoro sidelined following foot surgery, but left-back duo Luke Shaw and Tyrell Malacia remain short of fitness, while centre-backs Victor Lindelof and Will Fish are both ruled out too.
Harry Maguire started last week's FA Community Shield defeat to city rivals Manchester City, but after a troubled season in 2023-24, the England defender is still struggling to last 90 minutes.
Therefore, should Maguire miss out, fit-again Lisandro Martinez and 36-year-old Jonny Evans would vie with De Ligt for selection at the heart of United's back four.
Meanwhile, up front, Rasmus Hojlund's absence opens the door for ex-Bologna striker Joshua Zirkzee to make his first competitive start - though the Netherlands international did not take to the field at Wembley.
Mason Mount, Jadon Sancho or even captain Bruno Fernandes could instead be deployed in a false nine role, but Ten Hag has spoken of his reluctance to play Marcus Rashford through the middle.
It remains to be seen whether Ivorian winger Amad Diallo will retain his place this weekend, as Sancho, Antony and Alejandro Garnacho are all competing for selection across the final third.
Manchester United possible starting lineup: Onana; Dalot, De Ligt, Martinez, Mazraoui; Casemiro, Mainoo; Amad, Fernandes, Rashford; Zirkzee