United have fielded a changed team for every Premier League match so far this season and, on Wednesday evening, it was Lukaku and Pogbas turn to sit on the substitutes bench.
Both players started at St Marys at the weekend and badly struggled as Southampton held United to a 2-2 draw. After the clash, Mourinho is understood to have branded Pogba a virus in the changing room.
An injury crisis in defence meant Nemanja Matic and Scott McTominay were forced to start alongside Phil Jones on the south coast but Eric Bailly, Chris Smalling and Marcos Rojo have returned to the side to take on Arsenal.
Mourinho has opted for front three of Jesse Lingard, Marcus Rashford and Anthony Martial and the Portuguese defended his decision to ring the changes.
Asked if giving Rojo his first start of the season was a risk, Mourinho replied: I dont think gambling, I think sacrifice.
Theyre confident. I would never play a player if he has too many doubts. That was what happened against Southampton – too many doubts.
Theyre confident, ready for sacrifice that sometimes you need. The sacrifice that Jones had against Southampton and now its for others.
[Rojo] has zero minutes of competition all season. I think it is hard to play a game of this dimension but hes confident mentally, hes ready and very happy.
His first minutes would always come and by our needs come now and again Marcos is confident and ready.
While Lingard, Rashford and Martial were less than impressive against Young Boys, Mourinho believes the trio can cause Arsenal problems.
On his decision to drop Lukaku and Pogba, Mourinho replied: You know, [its] technical and tactical decisions.
Were going to play with Lingard, Rashford and Martial. We did that already before I think recently against Young Boys. We werent successful in goals we wanted to score but were happy with the situations we created.
In the first half versus Young Boys we didnt score but had big chances. [Theyre] young, fast, creative players even if theyre not what youd call “killer” when [they have a] chance to score a goal.