Spain's Santiago underwent an urgent operation for a detached retina on Thursday morning, the day his team was set to host Barcelona for a place in the Final Four.
The Euroleague MVP for March, Santiago has been Malaga's second-leading rebounder and scorer averaging 11.9 points and 4.9 rebounds this season.
After beating Barca 91-75 at home in game one of the three-game-series, Malaga lost in Barcelona 58-80.
The 2003 Euroleague champions Barcelona are trying to reach the Final Four for the second consecutive season, while Unicaja are attempting to reach their first European last four.
Juan Carlos Navarro scored 25 on 5-of-6 shooting from beyond the arc in under 19 minutes of play to lead Barca to victory in the second-leg, and Malaga are well aware that stopping the Spain point guard will be critical to their hopes of reaching the semi-finals.
"It's true that Navarro has played two great games lately against us and Tau in the Spanish League," said Malaga forward Carlos Jimenez.
"He is in a good moment. It will be almost impossible to keep him from scoring but we cannot forget about the rest of the players."
Barca coach Dusko Ivanovic said that his team had prepared for an altered Malaga game plan in the case of Santiago's absence.
"They play a different game without him and they can play with five small players. They are very aggressive on defense, especially when they play at home," he said.
"They have a lot of systems, but we have prepared our game for everything."
Follow LIVE coverage of the do-or-die quarter-finals between Malaga and Barcelona on www.eurosport.com from 20:45 CET and CSKA Moscow v Maccabi Tel Aviv from 18:15.