Head coach Mike Zimmer confirmed Bradford hurt his knee in the first half. However, Zimmer remained "hopeful" in regard to the quarterback's future availability.
Bradford missed three games at the start of the season due to a knee injury, although his health issues aren't as bad as they were earlier in his career.
Knee injuries limited him to just seven games from 2013-14, although he missed just two games because of injury over the next two seasons with the Philadelphia Eagles and Vikings. His only other absence was when he sat behind Shaun Hill for Week 1 last year.
When healthy, Bradford remains a consistent leader of the offense.
The 29-year-old set an NFL record with a 71.6 percent completion rate last season to go with 20 touchdowns and just five picks.
If he is forced to miss more time, veteran backup Case Keenum will return to the field while hoping the playmakers around him can carry the offense.