Case Keenum, who has thrown for 895 yards and four touchdowns this season (with no interceptions), will start again for the Vikings.
Bradford, who returned last week after missing three games, aggravated a knee injury late in the first half of Sunday's win against Chicago. Diggs has a groin injury, and starting left guard Nick Easton will also not play because of a calf injury.
Keenum finished with 140 yards on 17-of-21 passing and a touchdown with a 110.3 passer rating and 79.4 QBR in leading the Vikings to the 20-17 win over the Bears.
Diggs, who did not practice Thursday, said he "tweaked" his injury against the Bears. He was limited to 13 games last season because of a groin injury, which curtailed his ability to separate from defensive backs.
He leads the Vikings with 395 receiving yards on 23 receptions, which ranks second. His four touchdown receptions also leads the team.
Minnesota may increase Michael Floyd's workload in Diggs' place. Floyd was targeted one time in his return after a four-game suspension and had a critical 19-yard reception against the Bears.
ESPN Staff Writer Courtney Cronin contributed to this report.