Shakhtar just need a point, which would be a much easier feat if the Blues use the fixture to rest their top performers ahead of Sunday's Manchester derby.
City go into Sunday's derby with an extensive lead over United thanks to David Silva's 83rd-minute winner in the 2-1 victory over West Ham United.
To figure out the XI for Wednesday is an impossible job, but we do know that Yaya Touré and Ilkay Gundogan will be replacing Silva and De Bruyne in midfield.
"Ready for the match tomorrow!"
Pogba, who is serving a three-match domestic ban after receiving a red card in the win over Arsenal, said United must be ruthless in front of goal if they are to record their first win in three league games over City.
Demeaco Duhaney appears on the bench for the first time along with Brahim Diaz who will hope to make his third appearance for the senior team at some stage. "After that, we will see what happens".
Napoli play great football and it would be great to see them in the last 16, but they have made their own bed.
Even so, his starting line up was worth upwards of £280 million - while it also included two of their academy players - Phil Foden and Tosin Adarabioyo. That is now just one clean sheet in 14 Champions League away ties for City, and was the first time they'd gone 2-0 down in 34 games in all competitions.
Instead, the club have been looking for a replacement full-back and with January fast approaching, they're confident of landing long-term target Danny Rose. Should they lose, their progression will be placed in the hands of a pointless Feyenoord side tasked with holding a rampant Napoli team to an unlikely stalemate.
Taison fired wide and Yaroslav Rakitskiy fired a free-kick at Ederson as Shakhtar sought to make the result even more emphatic, but City grabbed a consolation from 12 yards in stoppage-time as Aguero smashed in a penalty.
And it was clear the Ukrainians had more riding on this game from the off. "We just play to win the game", Guardiola said. 5 SPOT SILVA: Can you see our Spanish midfielder after we won the 2011/12 Premier League, a clue - he is sporting some fancy headgear.
If there was nothing Ederson could do about that, he was largely at fault for another compatriot finding the net six minutes later.
Chelsea manager Antonio Conte, revealed after his sides 3-1 victory over Newcastle on Saturday that Eden Hazard is enjoying the extra freedom that his new central role allows him.