The 55-year-old actor was visibly surprised to learn on camera Tuesday that the 41-year-old actress and 52-year-old Big Short star are headed for divorce.
Clooney was attending the 2016 United Nations General Assembly in New York when CNN asked him to weigh in on his friends' split. The media outlet broke the news after Clooney revealed he didn't know "what's happened."
"I didn't know that. Wow. I feel very sorry, then. That's a sad story and unfortunate for a family," the actor said. "That's an unfortunate story about a family. I feel very sorry to hear that. That's the first I've heard of it."
Word had gotten out earlier in the day that Jolie filed for divorce from Pitt on Monday after two years of marriage and more than a decade together. The actress reportedly disapproves of Pitt's parenting methods with their six children.
"Angelina will always do what's in the best interest to protect her children," her manager, Geyer Kosinski, told E! News. "She appreciates everyone's understanding of their need for privacy at this time."
"I am very saddened by this, but what matters most now is the wellbeing of our kids," Pitt later said in a statement. "I kindly ask the press to give them the space they deserve during this challenging time."
Jolie and Pitt, who married in 2014, share four sons and two daughters whose ages range from 8 to 15. Model Chrissy Teigen, actor Josh Gad and television personality Brandi Glanville were among the other celebrities to react to the split.
Brad and Angelina. How am I supposed to go to work today ?— christine teigen (@chrissyteigen) September 20, 2016
PSA for all chicks Brad Pitt is officially single— Brandi Glanville (@BrandiGlanville) September 20, 2016