The funnyman stopped by "Conan" to plug his upcoming comedy "The Campaign," but he also took the opportunity to take a few choice jabs at the "Twilight" actress, calling her a "tramp-ire."
Stewart and Pattinson's relationship has been on the rocks in recent weeks after paparazzi snapped photos of the actress kissing her married "Snow White and the Huntsman" director Rupert Sanders.
Though host Conan O'Brien tried to comfort Ferrell, the comedian was positively distraught over the news that the tween icons' love affair may be kaput.
"What they had was so special Conan," Ferrell said, while tearing up. "You don’t even know what they had. They were, they were in love and she just threw it all away."
"It’s not going to be fine ever," he added.
But as the last embers of Pattinson and Stewart's once red-hot passion die out, Ferrell was left with only questions and self-recriminations.
"I don't know if there was anything I could have done to prevent it," Ferrell said. "I don’t know what it means to the ‘Twilight’ franchise. I just don’t know."
Watch the full clip below: