That according to Cowboys owner Jerry Jones, who said Bryant is out for the rest of the season with a fractured right ankle.
"That sets us back," Jones said. "That sets us back. I really feel bad for him, but it really sets us back. The good news is we've got some depth there. That'll give (Kevin) Ogletree and guys like that a little more play time."
Bryant has been dealing with a bothersome right ankle all season since injuring it in training camp. He was playing against the Colts with a bruised back as well as a sprained left ankle suffered during practice Friday.
A rookie from Oklahoma State, Bryant has 45 catches for 561 yards and six touchdowns this season.
"He's certainly made great strides in his rookie year," Dallas coach Jason Garrett said. "For a guy who missed as much training camp as he did to make the impact he's made on our football team has been significant."
The Associated Press contributed to this report.