When Nick Saban retired, Ole Miss head coach Lane Kiffin lost his favorite off-field rival. Now, it's Brian Kelly leading the LSU Tigers into the spotlight.
Kiffin has taken just one of their three head-to-head matchups, and that lone upset still lingers heading into this weekend. The question is: did Kelly learn from that loss two years ago on this same road trip?
My LSU vs. Mississippi predictions and college football picks believe Kelly did. Kickoff comes at 3:30 p.m. ET on Saturday, September 27.
LSU vs Mississippi prediction
LSU vs Mississippi best bet: LSU moneyline (+102)
Two years ago, Brian Kelly and the LSU Tigers went to Oxford and found themselves in a shootout, losing 55-49 despite being 2.5-point favorites. In the other two matchups between Kelly and Kiffin, the Under cashed as LSU won both outright and against the spread.
That may not sound entirely applicable as both these rosters enter this weekend with flaws and questions, but the styles of the two coaches determine their teams more than may be true of most programs. Kiffin will always be a chaos agent thriving on variance, while Kelly will always try to control every variable he can.
Controlling variables with this LSU team, particularly against this version of the Mississippi Rebels, should mean shortening the game and trusting the Tigers’ defense despite all preseason expectations of a national-title caliber offense led by quarterback Garrett Nussmeier.
LSU’s offense ranks No. 60 in expected points added (EPA) per snap, far from a threat, but its defense brings enough aggression that it should fluster Rebels’ newfound starting quarterback Trinidad Chambliss.
Throwing unique wrinkles at a quarterback making his second FBS start should provide Nussmeier a short field or two, and that edge should mesh with Kelly’s need for control.
LSU vs Mississippi same-game parlay
Kelly will do all he can to avoid a shootout with Kiffin. Kelly learned that the hard way two years ago in Oxford.
Forcing the ball out of Chambliss' hands will help that cause, not that Mississippi really minds handing off to Kewan Lacy, given he has cleared this prop in three of four games this season.
LSU vs Mississippi 3-leg SGP
- LSU moneyline
- Under 54.5
- Kewan Lacy Over 67.5 rushing yards
Our deep-ball SGP: Wallace left wanting for more
Backup quarterbacks are often exposed in their second and third games as defensive coordinators see on film why they were backup quarterbacks in the first place. If that fate comes to be reality for Chambliss, it may be at receiver Harrison Wallace's expense.
LSU vs Mississippi 4-leg SGP
- LSU moneyline
- Under 54.5
- Kewan Lacy Over 67.5 rushing yards
- Harrison Wallace III Under 71.5 receiving yards
LSU vs Mississippi game predictions
LSU vs Mississippi moneyline prediction
LSU is more talented than Mississippi this season, despite the September struggles from the Tigers’ offense. Putting some faith in preseason expectations of LSU may seem bold, but what have the Tigers really done to dissuade us? Not blown out Clemson and Louisiana Tech?
LSU may have been biding its time.
LSU vs Mississippi spread prediction
If taking the moneyline underdog outright, then the spread thoughts should be obvious. Realize that any game with a spread of -1.5 is effectively the result of oddsmakers saying this should be a pick’em, but they need to move the juice around a bit.
The “six-pack” on the odds board — moneyline favorite, moneyline underdog, take the points, lay the points, Over, and Under — needs all pieces filled to look right. A spread of -1.5 is an effort at that optical offering as much as anything else.
That said, in the era of more two-point conversions, a spread of -1.5 comes into play more often. Both these coaches have a propensity to try for two for a win. And in both instances, that lends further value to the +1.5 underdog.
LSU vs Mississippi Over/Under prediction
If LSU gets into a shootout, it may have the more veteran quarterback, but the Tigers will need to worry. Kelly needs to slow this game down. Some thought was put into betting on Garrett Nussmeier’s first-quarter passing yards Under of 65.5 at FanDuel, simply because Kelly and LSU will be best served by tightening this game from the outset.
LSU vs Mississippi odds
- Spread: LSU +1.5 | Mississippi -1.5
- Moneyline: LSU +102 | Mississippi -122
- Over/Under: Over 54.5 | Under 54.5
LSU vs Mississippi trend to know
LSU’s three games against FBS opponents have not only all gone Under their totals, but they have done so by an average of 21.8 points. Find more college football betting trends for LSU vs Mississippi.
How to watch LSU vs Mississippi
| Location | Vaught-Hemingway Stadium, Oxford, MS |
| Date | Saturday, September 27, 2025 |
| Kickoff | 3:30 p.m. ET |
| TV | ABC |
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Odds are correct at the time of publishing and are subject to change.
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