The 62-year-old Francona has been wearing a walking boot on his right foot for most of the season after having toe surgery for a staph infection in February. He also is dealing with a hip issue that will require surgery.
"It's not just been hard physically, it's been really hard mentally," Francona told reporters Thursday. "I think the coaches knew that it had been weighing on me for a while. Man, it's difficult.
"A big reason why it's difficult is because I love what I do and I love where I do it. I love this place. When people talk about our organization, I want them to talk with pride, because that's how I feel. I don't want that to ever change."
This is the second consecutive year in which Francona, who won two World Series championships with the Boston Red Sox, has been sidelined because of health problems. He managed the Indians for just 14 games in 2020 because of a serious gastrointestinal issue that caused him to stay in the Cleveland Clinic for multiple weeks.
While hospitalized, Francona experienced blood-clotting issues, and he was placed in intensive care. First base coach and former Indians star catcher Sandy Alomar filled in for Francona during that season.
Bench coach DeMarlo Hale will take over on an interim basis for the rest of the 2021 campaign while Francona improves his health. Third base coach Mike Sarbaugh will take Hale's role, and assistant coach Kyle Hudson will switch to third.
Francona, who guided the club to the World Series in 2016, is in his ninth season with the Cleveland Indians. He has produced a winning record each year, and he is only five wins away from tying Hall of Famer Lou Boudreau (728) for the most victories in franchise history.