Louisville football is taking on the SMU Mustangs this weekend, and with the Cardinals fans hoping for another nine-win season, this road game is set to be a huge challenge for Jeff Brohm's Cardinals. SMU is one of the top teams in the ACC, as the Mustangs are 7-3 on the season, but 5-1 in the ACC.
The Mustangs and the Cardinals both defeated Miami this season, giving the Hurricanes their two losses. Now, in this crucial matchup as SMU tries to keep its ACC Championship dreams alive, and Louisville tries to play spoiler, the Cardinals are given a massive obstacle as the injury bug hit them hard this weekend.
The ACC released its first injury report for this showdown, and the Cards fans did not like what they saw, as Louisville will be without three stars, including its top two running backs.
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Louisville football gets crushed by the injury bug for SMU showdown
The Cardinals fans learned late Thursday night from the first injury report that not only will Isaac Brown be sidelined for his third straight game, but Louisville is also down rising star Keyjuan Brown and key linebacker Antonio Watts.
Louisville will be without running backs Isaac Brown and Keyjuan Brown and linebacker Antonio Watts on Saturday vs. SMU, sources tell @On3sports.
— Pete Nakos (@PeteNakos) November 21, 2025
Watts has 6.5 tackles for loss and 3 INTs this season. Brown’s status is unclear for next week at Kentucky.… pic.twitter.com/h9zw8RrVqf
Louisville's gut-wrenching injury update leaves only Duke Watson available for this Cardinals matchup with the Mustangs, and he has been battling injuries all season. The Cardinals are coming off a heartbreaking 20-19 loss to Clemson, and clearly, the extra day didn't help them get healthy, as fans saw many key players on the initial injury report.
Also, on the injury report, Miller Moss is listed as questionable. The Cardinals quarterback has started every game this season and, despite an up-and-down season, has been Louisville's No. 1 option throughout. The Cardinals' defense got a massive boost last week as Stanquan Clark returned to action, and his name isn't on the injury report for the first time since his ankle injury in Week 2.
However, this offense got crushed by injuries this weekend, and playing on the road against a good ACC team makes this a massive challenge for Brohm and the Cardinals. Isaac and Keyjuan have been two stars on Louisville's offense and among its best players. This team went on a run and was playing through these two stars and this rushing attack, but Isaac went down and Louisville fell in both games without him on the field, and now Keyjuan is out after rushing for 95 yards or more in four straight games and 135 yards or more in both games he was RB1.
It is going to be a tough challenge to win on the road without these three stars, but Brohm pulled off a massive upset against Miami. He could do it again, this time against SMU.