Michael Carrick provided an update on the pair in the news conference on Monday evening, confirming the the double fitness blow.
"They've not travelled, they both picked up issues in the game on Saturday [against Spurs] and we were working through that, to see what that looks like," he said.
"At the moment, they are not ready for the game tomorrow."
Luke Shaw will miss out for Manchester United in Spain
Getty
Therefore, Carrick could move first-choice right-back Diogo Dalot to the opposite flank, thus making minimal changes to the defence that started at the weekend.
Alternatively there is also the option of moving Lisandro Martinez across or handing a start to Ayden Heaven or fellow youngster Harry Amass.
In midfield, United are well placed to cope if Mainoo has to miss out. Carlos Baleba could make his full debut after a substitute appearance against Spurs and Andrey Santos is pushing for more minutes having not featured in the two games either side of the international break.
Bryan Mbeumo put forward his case to continue up front, in the absence of Benjamin Sesko, with a goal at the weekend but Amad Diallo and Matheus Cunha are at risk of making way for Marcus Rashford and Joshua Zirkzee.
Predicted Manchester United XI: Lammens; Yoro, Maguire, Martinez, Dalot; Tielemans, Baleba; Amad, Fernandes, Cunha; Mbeumo
Injured: Ugarte, Dorgu, Sesko, Mazraoui, Heaton, Shaw, Mainoo
Time and date: 8pm BST on Tuesday, October 13, 2026
How to watch: Amazon Prime
Venue: Metropolitano Stadium