Neymar was injured during a French League match and is ruled out of the second leg match of the Champions League.
The teams meet on Tuesday at Parc des Princes in Paris, with PSG trailing 3-1 after capitulating late in the first leg of the round of 16.
For several seasons now, some PSG players have talked themselves up as good enough to win the Champions League. Yet the hard fact staring back at them from the gilded mirror is that, despite enormous investment from Qatari owners QSI for nearly seven years, PSG has never been beyond the quarterfinals in that time. Its lone semifinal appearance was way back in 1995.
This season feels like make-or-break for PSG to be taken seriously as one of Europe's elite clubs. But there is a huge hurdle to overcome first: Madrid.
With three Champions League titles in the past four years, and 12 overall, Madrid are precisely the club PSG dream about becoming one day.
But coach Unai Emery's side must first focus on turning around the 3-1 deficit - and doing so without Neymar, who was injured on Feb. 25 in a French league game against Marseille.
The Brazil forward is recovering from surgery on his right foot and may not even play again for PSG this season.
PSG splashed out a world record 222 million euros ($260 million) to sign Neymar from Barcelona. They spent another 180 million euros ($216 million) on Kylian Mbappe from Monaco but the 19-year-old forward is doubtful as he recovers from a cut to his right ankle. Should Mbappe fail to play, it might not be all bad news for PSG.
It would almost certainly mean a front three of Julian Draxler, top scorer Edinson Cavani and Angel Di Maria, who has scored 13 goals since January.
They tore Barcelona apart last season when PSG won 4-0 at home in the first leg of the last 16. But this summer's arrival of Neymar and Mbappe put a swift end to that promising attacking trio.
PSG's firepower has never been the issue, however. The real problem is keeping goals out.
A lack of composure in big games has often undone PSG, notably last season when the club made history by becoming the first club eliminated after winning the first leg 4-0. Barcelona's 6-1 victory in the return will haunt PSG until they prove capable of coming through big games, starting with Tuesday's encounter.
PSG's fragile defence conceded two late goals in Madrid and will have to cope with the return to top form of Cristiano Ronaldo.
He is the competition's all-time leading scorer and current top scorer with 11, including two in the first leg. The Portugal forward set a record on Saturday by becoming the fastest to reach 300 La Liga goals.
Madrid got a further boost with midfielders Luka Modric and Toni Kroos returning to training on Sunday. Neither has played since picking up knocks in the first leg.
There is little suspense in Tuesday's other Champions League game. Five-time champion Liverpool are at home to two-time champions Porto, having won 5-0 away.
Liverpool manager Juergen Klopp could even rest many of his senior players for the second leg on Tuesday, with star forward Mohamed Salah allowed to play the full 90 minutes against Newcastle in the Premier League on Saturday evening.
Winning the Portuguese league might be Porto's priority now - it is five points clear after a 2-1 win over Sporting on Friday.