The Argentina international sustained a thigh injury in PSG's 2-0 Ligue 1 win over Marseille on Monday (AEDT).
Head coach Mauricio Pochettino says the 32-year-old will be unavailable for the match at Camp Nou on February 16, as well as the Coupe de France game at Caen on Wednesday and Saturday's league clash at home to Nice.
"As the club said, there'll be further communication within the week concerning Angel but his participation in the match against Barcelona is compromised," Pochettino said on Tuesday of Di Maria.
The former Manchester United and Real Madrid player has been directly involved in 14 goals in all competitions this season, behind only Neymar (16) and Kylian Mbappe (27) within the PSG ranks.
"His absence isn't a reason to change our ideas," Pochettino said. "We'll find the best available solutions. Angel has played a lot and he's an important player for us. But there are other players who can play and enable us to win matches."
Pochettino plans to resist the temptation to rest too many of his star names for the cup match at Stade Michel-d'Ornano despite the importance of the Barca tie.
PSG will certainly be without Marco Verratti (hip), Colin Dagba (thigh), Juan Bernat (knee) and Timothee Pembele (coronavirus protocols), while goalkeeper Keylor Navas is only expected to return to team training the day after the game.
There are also doubts over Mauro Icardi, who is nursing a bruised thigh, and Ander Herrera, who only this week resumed training after a month out with a muscle problem.
However, Pochettino is determined to field a strong enough side to reach the next round rather than simply use it as an opportunity to rotate and experiment with his tactics.
"We're not testing things in other competitions," he said. "We need to perform in all competitions. Against Caen, we'll need to play the best we can in order to win.
"We're going to take the best decisions in order to be competitive against Caen. That's our first objective. I'll analyse today the condition and the fitness of each player. We'll say who is available and take into account the risk of injury.
"We're going to select the best possible team, with players who are at 100 per cent, in every position, in order to win the match."