The Red Devils head to Ashton Gate on Wednesday as the massive favourites to progress to the semi-finals as they come up against Championship opposition in the Robins.
However, with Bristol currently amongst the second division’s top three and challenging for a place in the Premier League next season, Mourinho is set to take no chances with his team line-up.
However, when asked about the likeliness of the seemingly-forgotten Henrikh Mkhitaryan getting a run-out, Mourinho said: "He can. I am making a few changes for the match, not many, because Bristol is one of the best teams in the Championship and for me now the Championship is not the Championship of five or 10 years ago.
"The Championship is now high-quality teams with lots of players that could be playing in the Premier League easily. So we need to take the game really seriously. But I am going to make a few changes and it's possible Mhiki is involved.
"At the moment we are playing (Juan) Mata, (Marcus) Rashford, (Jesse) Lingard or (Anthony) Martial, (Romelu) Lukaku and the bench has been Ibra and one of the other ones - Martial or Rashford.
"There is no space for everybody because you need balance on the bench too."