United welcome their French opponents to Old Trafford for the first leg of the last-32 tie but the hosts will be without their skipper, who is struggling with a minor muscular injury.
Rooney, who has been linked with a move away from the 20-time English champions, could be back in time for Sunday’s FA Cup fifth-round encounter away at Blackburn Rovers.
England international Michael Carrick is also out of Thursday’s clash after picking up a similar issue to the captain, while defender Phil Jones is absent after sustaining a foot injury in the 0-0 draw with Hull City on February 1.
Left-back Luke Shaw will also be missing after he suffered another setback and this will be the fourth consecutive game the 21-year-old has been left out of the first-team squad.
Antonio Valencia, Eric Bailly, Chris Smalling and Daley Blind are expected to start at the back after receiving praise from manager Jose Mourinho although Marcos Rojo is also available for selection.
Marcus Rashford and Anthony Martial will both be pushing for starts while former Sweden international Zlatan Ibrahimovic, who has scored 20 goals in all competitions since joining the club last summer, is set to lead the line once again.
Champions Manchester City put on a show at the Etihad Stadium as they swept Swansea aside with a five-goal demolition.
Antonio Conte watched his Chelsea side defeat Southampton 2-0 to reach the FA Cup final and then made Manchester United favourites.
Rony Lopes has refused to rule out a future return to Manchester City despite claiming he remains fully committed to Monaco.
Chelsea will meet Manchester United in next month's FA Cup final following a 2-0 win over Southampton.
Sam Allardyce says securing a top-10 finish in the Premier League is Everton's main priority for the remainder of the season.
Michel Vorm claims Tottenham are disappointed they will end another season without a trophy but he is confident success will come.
Hoffenheim manager Julian Nagelsmann insists he will not be joining either Arsenal or Chelsea in the summer.
Liverpool manager Jurgen Klopp believes Danny Ings will continue to score goals in the Premier League now he is fully fit.
PSV Eindhoven technical director Marcel Brands is thought to lining up a couple of Eredivisie targets as he plots for life at Everton.
Marseille enjoyed an impressive 5-1 victory over Lille on Saturday, but the win came at a cost due to an injury to Hiroki Sakai.
