Paris St-Germain boss Thomas Tuchel has confirmed Edinson Cavani will not face Manchester United due to a hip injury.
Fellow forward Neymar is already ruled out of Tuesday’s first leg and the return game on 6 March through injury.
Tuchel says Cavani’s absence at Old Trafford is an additional blow.
He said: “Would Man Utd miss Pogba or Rashford? Of course. Neymar is one of our best players and one of the best players in Europe. We will miss him a lot. And now Cavani is out.”
The 31-year-old injured a tendon in his hip after scoring a penalty in Saturday’s 1-0 victory over Bordeaux.
Neymar is out for 10 weeks with a broken metatarsal suffered in a 2-0 French Cup victory over Strasbourg on 23 January.
That leaves World Cup-winning forward Kylian Mbappe – who replaced Cavani at the weekend – as the only fit member of their first-choice front three.
“You can’t place all the burden on Mbappe. It’s not his job to replace Cavani and Ney,” said Tuchel.
“He has to be free to play his game. I want us to provide him with the right kind of support. He needs to play with a good mindset and to be positive.
“We are here to score, perhaps more than one.”
Right-back Thomas Meunier is also out of the first leg with concussion but Marco Verratti is fit after an ankle problem.
United have almost a fully-fit squad, with Antonio Valencia and Matteo Darmian the only injury absentees.
Marcus Rashford, Alexis Sanchez and Jesse Lingard could be recalled after they were dropped to the bench for Saturday’s win at Fulham.