It will be the first missed game this season for Claypool, who expressed frustration Friday with his usage in the offense.
The Bears are also making an adjustment to their depth chart at quarterback, where rookie Tyson Bagent will now back up Justin Fields. Nathan Peterman served as Fields' primary backup in the Bears' first three games but is inactive against the Broncos.
Claypool said Friday that he did not think he has been put in the best position to showcase his skill set, saying he has "been adapting to the new system and my new role in the system and trying to make the most out of it."
Claypool's comments came weeks after he drew criticism -- and subsequently apologized to the coaching staff and teammates -- for a lack of effort in the opener against the Green Bay Packers. His lack of execution and effort with run blocking and the screen game had been addressed by Bears coaches and players throughout the week following that loss.
Bears wide receiver Equanimeous St. Brown is active for the first time this season.
"We'll see where it is," Bears coach Matt Eberflus said Friday when asked about St. Brown's availability for Week 4. "There's definitely an opportunity there. We'll see where it is. We'll make those decisions here in the next few hours, and yeah, we certainly like the way he practiced."
The winless Bears are averaging 15.7 points per game in losses to the Packers, Buccaneers and Chiefs. Claypool has been targeted 14 times and has come away with four catches for 51 yards and a touchdown.
Claypool, 25, is in the final season of his rookie contract. In 10 games with Chicago after being traded from Pittsburgh in November 2022, Claypool has struggled to establish a high-volume role, having caught 18 passes for 191 yards and one touchdown.