After more than 18 Emmy wins, the final scenes of the eighth and final season have been filmed and Kiefer - who stars as federal agent Jack Bauer - said the cast and crew had become a family.
He said: "I think over the course of the eight years, we've had 16 marriages and 30-something children have been born. We were like a family. So, it's very hard to say goodbye."
However the actor conceded the time was right to end the real-time drama.
"Howard Gordon [the executive producer]... normally halfway through the season will say, 'I've got a great idea for next year.' And he just wasn't feeling it," he said.
Kiefer's co-star Mary Lynn Rajskub, who plays Jack's colleague Chloe O'Brian, was also saddened by the show coming to an end.
Recalling her final day on set, she said: "When they said, 'Cut!', I don't know what I was thinking. And then they said, 'This is Mary Lynn's series wrap.' And I just looked around. The crew was surrounding me. And I just kind of burst into tears."
Mary Lynn also dropped a few hints about the final episode, which is due to air on Sky1 on June 6.
"Right now, we see Chloe having to come up with Jack and go after him, and go against his wishes, which she's never really done," she said.
"She's being put in this position of power and having to grapple with these decisions that she's never had to do before, so she decides to take it on herself and go find him and confront him, and it's pretty explosive."