Kyler Murray returned to practice on Friday, but he likely won't be healthy enough to play two days later.
While the Cardinals are leaving the door open for Murray and won't make a final decision until Sunday morning, they are preparing for Jacoby Brissett to start against the Colts, NFL Network Insiders Ian Rapoport, Tom Pelissero and Mike Garafolo reported.
Rapoport added that Murray is dealing with a mid-foot sprain, which is a version of a Lisfranc injury, and that there is a possibility he sits beyond this week since pushing it can cause an aggravation.
The 28-year-old missed two offensive plays of a Week 5 loss to the Tennessee Titans, going to the blue tent and then the locker room for evaluation after diving to recover an errant snap that struck him in the facemask. He sat out the first two practices of the week before returning in a limited fashion Friday, but Arizona looks to be ready to hold him out so he can heal.
Through five games in 2025, Murray has been streaky, with an 88.6 passer rating and 68.3 completion percentage while throwing for 962 yards, six touchdowns and three interceptions. He's also rushed for 173 yards and another score.
Murray's likely absence is nonetheless a massive blow for the Cardinals, who have suffered three brutally close losses in a row (by a combined five points), are also down their top two running backs and now must keep pace with the NFL's No. 2 scoring offense in Indianapolis.
Brissett, 32, has a 19-34 career record split between six teams, most recently going 1-4 under center for the New England Patriots last season with 826 passing yards, two touchdowns and one interception. He's capable of distributing to Arizona's top targets, wide receiver Marvin Harrison Jr. and tight end Trey McBride, but the offense's ceiling in terms of explosiveness likely lowers considerably.
If Murray ends up needing to miss time beyond this weekend, the Cardinals have a home game against the Packers in Week 7 before their Week 8 bye.
For now, they'll look to stop the losing streak at three when they take on the Colts (4-1) at 1 p.m. ET on Sunday.