United haven't won any of their last three league games and languish down in eighth in the table, a huge 19 points off leaders Manchester City.
Even qualifying for next season's Champions League will be a struggle for Mourinho's men as they trail fourth-placed Arsenal by eight points ahead of Wednesday's meeting at Old Trafford.
Lukaku scored his first club goal since September in Saturday's 2-2 draw at struggling Southampton but was otherwise largely ineffective, while Pogba's performance drew stinging criticism amid rumours of another dressing room bust up with Mourinho.
In total Mourinho has made seven changes to the side that started on the south coast with defender Marcos Rojo making his first appearance of the season after a long-term knee injury.
Arsenal boss Unai Emery makes just one change from Sunday's thrilling 4-2 derby win over Tottenham as Aaron Ramsey replaces former United midfielder Henrikh Mkhitaryan.
Mesut Ozil is again not even included in the Gunners' squad as Arsenal look to extend their impressive unbeaten run to 20 games.