Louisville meets Mississippi on Sunday at Nissan Stadium in Nashville, Tennessee, in the Week 1 main event in college football. After all, this is the only game this week featuring two top-25 teams.
I explain why the price for the Cardinals is disrespectful, considering the unknowns with the Rebels heading into this season, in my Louisville vs. Mississippi prediction.
Check out all of our college football picks for the opening weekend matchup on Sept. 6.
TOP PICK
Who will win Louisville vs Mississippi: Louisville +6.5
Do we know if the Mississippi Rebels' first-year head coach Pete Golding is good? He was promoted to head coach right before the 2025-26 College Football Playoff (CFP) after Lane Kiffin went to LSU.
The Rebels hammered Tulane in the first round of the CFP, upset Georgia in the Sugar Bowl and nearly beat Miami in the Fiesta Bowl, which was the CFP semifinals. But if it lost to Tulane, or if Georgia took care of business, would Mississippi have hired Golding?
This is his first head coaching job and going from a coordinator to a head coach of an SEC team that was a few plays away from being in the national championship is a huge jump professionally.
That said, I have a tough time accepting Mississippi as a -6.5 favorite vs. the Louisville Cardinals on a neutral field. Plus, do you know who beat Miami last season? The Cardinals on the road as +13 underdogs.
Three of their four losses last year were by three or fewer points and two were in overtime. Louisville finished tied for 23rd in net adjusted EPA/play last season, which adjusts for opponent strength and removes garbage time, and 17th in net yards per play, per GameOnPaper.com.
COVERS INTEL: According to VSIN, Louisville Cardinals head coach Jeff Brohm is 11-4 ATS as an underdog of 7+ points since 2018, dating back to his days with Purdue. 
Louisville vs Mississippi Over/Under pick: Under 55.5
Since hiring Brohm in 2023, the Cardinals are 2-6 Over/Under against ranked teams. Only two of their offensive starters played on last year's team, and Ohio State transfer QB Lincoln Kienholz makes his team debut Sunday.
Golding was a long-time defensive coordinator, which probably makes him a more conservative playcaller than Kiffin, and Ole Miss has more defensive continuity year over year. The Rebels lost five of their top-six receivers, so they should run more, at least in Week 1, which means more running clock.
Louisville vs Mississippi combo
Simply put, Under bets correlate with underdogs for obvious reasons. Although I'm less confident in the Under leg in my combo, this is a national TV game, which could lead to tightness for both teams. Also, the Under is 4-1 in Louisville's last five games as an underdog.
Louisville vs Mississippi combo
- Louisville +6.5
- Under 55.5
Louisville vs Mississippi odds
For help understanding probabilities, see our odds calculator.
- Spread: Louisville +6.5 (48%) | Mississippi -6.5 (52%)
- Over/Under: Over 55.5 (47%) | Under 55.5 (53%)
- Moneyline: Louisville 30% | Mississippi 71%
For the full slate of college football matchups, check out our college football odds board!
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Louisville vs Mississippi weather
In Nashville Sunday, temperatures are projected in the upper-80s with 10 mph winds and zero chance of rain.
Check out our college football weather page for up-to-date info on every matchup.
Louisville vs Mississippi trend to know
The Cardinals are 4-1 ATS in their last five games as an underdog. Find more college football betting trends for Louisville vs. Mississippi.
How to watch Louisville vs Mississippi
| Location | Nissan Stadium, Nashville, TN |
| Date | Sunday, Sept.6, 2026 |
| Kickoff | 7:30 p.m. ET |
| TV | ABC |
Louisville vs Mississippi latest injuries
Check out our college football injuries page for updates on every team.
Odds are correct at the time of publishing and are subject to change.
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