Kentucky Wildcats vs Louisville Cardinals Prediction, Odds and Picks for Saturday, 11/29/25

One of the more underrated rivalries in college football comes in Kentucky, where the Louisville Cardinals are set to host the Kentucky Wildcats in a game that features a ton of uncertainty due to injuries. On one side, the Kentucky injury report figures to be pretty lengthy this week, as the Wildcats have dealt with plenty of attrition on both sides of the ball, particularly in the defensive backfield. And while the injuries have certainly added up on defense — and it showed in last week’s blowout loss to Vanderbilt — the Wildcats are also dealing with injuries within their wide receiving corps and the tight end room heading into this game. That doesn’t bode well against a Louisville defense that is one of the best units in the ACC and has largely held up its end of the bargain in recent weeks, even as the Cardinals offense has struggled mightily during this demoralizing 3-game losing streak.

On the topic of the Louisville offense, Jeff Brohm’s unit has gone downhill fast in recent weeks. It all started with the injury to running back Issac Brown, who is the engine behind the success of the Louisville offense this season. Not only did the Cardinals lose at home to California as a massive favorite, they followed that up with a brutal 1-point home loss Clemson in a game that Louisville had every chance to win. Last week, the Cardinals hit rock bottom by starting a backup quarterback in place for the injured Miller Moss and finishing with just 6 points in a drubbing at the hands of a red-hot SMU team on the road. While this week would ordinarily be a good spot to back Louisville at home following that embarrassing loss, its hard to gauge just where Brohm and his team are at mentally, especially since the Cardinals will likely be without Moss, along with their top 3 running backs and star wideout Chris Bell. Even against a Kentucky defense that will be without a number of key contributors this week, it’s hard to see Louisville rack up many points in this one. With that in mind, the under is my preferred play on this contest.

Kentucky vs Louisville prediction: Under 47.5 available at time of publishing. Playable to 47.

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