United face Championship opponents for the third round in a row as we make the short trip to struggling local rivals Blackburn for a place in the quarter-finals.
Having dispatched second-tier sides Reading and Wigan by the same 4-0 scoreline, the holders hit the road for the first time in this season's competition to meet Owen Coyle's injury hit Rovers.
The Reds have never retained the famous trophy and with one foot in the last 16 in Europe and the EFL Cup on the horizon, Jose is likely to stick to his rotation policy of the previous ties.
In contrast to many of his top flight peers, the boss has insisted he's taking United's Cup defence seriously and despite changes, looks set to name a strong side at Ewood Park.
"We played already two teams from the Championship so it is not new for us to play an opponent from this level and difficulty.
"One thing is Old Trafford, it is another to go away so I go serious and we will have a strong side.
"I'm going to change a few players but it will be a good team because I respect the competition a lot, and Manchester United demands that you go serious for every game so we shall do that.
"If we lose, we lose, but it will not be because we throw the game away.
"Sometimes the opponent is better or you don't play well but we will go to Blackburn with respect."
United will be strong favourites to reach the last eight, with our five clean sheets in a row coupled with Blackburn's focus on their battle for survival in the Championship.
Rovers come into this tie one place off the bottom and three points from safety after a 2-1 defeat at promotion-chasing Sheffield Wednesday last time out.
They go into this fifth round encounter with a host of injuries and unavailable players and sit one place off the bottom of the table, two points from safety.
Wayne Rooney and Michael Carrick are expected to be available after slight injuries but Henrikh Mkhitaryan and Phil Jones are both doubtful.
Elliot Bennett and Hope Akpan are suspended for the hosts with Lucas Joao cup-tied, while top scorer Sam Gallagher is out with a knee injury.
Ex Red Corey Evans, Adam Henley and Elliott Ward will all miss out but former United legend Wes Brown could feature.
Form guide: Blackburn D W L W D L United L W D W W W
Match odds: Blackburn 17/2 Draw 15/2 United 1/3
Referee: Martin Atkinson