Milan coach Massimiliano Allegri said the loss of the volatile Swede, who fell out with Barca coach Pep Guardiola and was offloaded at the end of the 2009-10 season, was a severe blow and he was as important to the Italian side as Argentine World Player of the Year Lionel Messi was to Barca.
"Unfortunately this morning at the end of training Ibra felt a twinge in his adductor and he has remained at home," Allegri told a news conference, adding that the player was also doubtful for his side's Serie A match at Napoli this weekend.
"They (Ibrahimovic and Messi) are two champions with different characteristics but within the two teams they have the same value," he said.
"It's a big loss but we have to go out on to the pitch and play regardless."
Both teams come into the match having drawn 2-2 in their domestic leagues at the weekend. Seven-times European champions Milan were held at home to Lazio, while Barca, the four-times winners and holders, drew at Real Sociedad.
Allegri is also without Italian striker Filippo Inzaghi and Brazil forward Robinho and may opt to strengthen the midfield and play with only one out-and-out forward in Robinho's international team mate Alexandre Pato.
"Of course Ibra for us is a very important player, he has very special qualities," Milan's Netherlands midfielder Mark van Bommel said at the same news conference.
"But not only Ibra we have a few players who are injured."
Van Bommel was bombarded with questions from the Spanish media about what they portrayed as his brutal performance in last year's World Cup final, when Spain won 1-0 with a dramatic goal in extra time scored by Barca midfielder Andres Iniesta.
The match was littered with fouls and yellow cards and Van Bommel clashed with Iniesta near the end of the game.
"We were playing the final of the World Cup," the Dutchman, a former Barca player, said.
"Everybody wants to win and of course you are fighting with a player or several players and not just me.
"I don't have hard feelings against Iniesta. I played with him for one year and after the match I forgot everything and I think Iniesta and all the other Barca players like Xavi and Victor Valdes as well.
"That's football and tomorrow is another match. Maybe tomorrow we see each other again on the pitch. I hope so."
Iniesta told an earlier news conference there had been some strong challenges in the final in Johannesburg but he said it was all in the past.
"In that sense I don't want to keep dwelling on the issue. I don't think I have had any problem with any team mate I have shared a dressing room with.
"I don't think anything will happen again tomorrow."