Louisville Cardinals vs Pittsburgh Panthers Prediction, Odds and Picks for Saturday, 09/27/25
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Louisville vs Pittsburgh Pickswise Expert Predictions
The Louisville Cardinals are off to a 3-0 start but are 0-3 against the spread, taking on a Pittsburgh Panthers squad fresh off a bye week after falling to their rival West Virginia. Both squads enter this game ranking top-30 in total defense and top-35 in defensive efficiency. On the contrary, both offensive units fall outside the top-70 in efficiency.
Louisville and Pittsburgh both possess talented backfields, and I expect them to lean on the run game behind Isaac Brown and Keyjaun Brown for the Cardinals and Desmond Reid for the Panthers. For what it’s worth, the total has gone under in 3 of the last 4 meetings between these teams, and I expect the small sample size trend to continue; I’ll take the under.
Louisville vs Pittsburgh prediction: Under 57.5 (-110) available at time of publishing. Playable down to 56.5 (-110).
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Ryan Bunnell
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