LSU vs. Ole Miss Prediction, Odds and Key Players to Watch for College Football Week 5

Betting odds, pick and prediction for the LSU vs. Ole Miss matchup in Week 5 of the college football season.

LSU Tigers quarterback Garrett Nussmeier is looking to lead his team to a 5-0 start. / Stephen Lew-Imagn Images

A pair of undefeated SEC teams go head-to-head in Week 5 as the No. 4 LSU Tigers hit the road to play No. 13 Ole Miss.

LSU has some impressive wins on the schedule already this season, as it knocked off Clemson in Week 1 (on the road) before beating Florida at home in Week 3. Both of those teams have struggled in 2025, but they were ranked heading into the 2025 season.

Meanwhile, Ole Miss has battled an injury to starting quarterback Austin Simmons, riding Trinidad Chambliss to a 4-0 start. Chambliss leads the SEC in yards per completion and yards per attempt in the 2025 season.

Oddsmakers have set Lane Kiffin’s Rebels as favorites at home, but both of their SEC wins (over Arkansas and Kentucky) have come by just one score.

Can potential Heisman candidate Garrett Nussmeier enter into a hostile environment and lead the Tigers to a road win?

Let’s dive into the odds, a key players to watch and my prediction for this SEC battle in Week 5. 

LSU vs. Ole Miss Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• LSU +2.5 (-105)
• Ole Miss -2.5 (-115)

Moneyline

• LSU: +114
• Ole Miss: -135

Total

• 55.5 (Over -108/Under -112)

LSU vs. Ole Miss How to Watch

• Date: Saturday, Sept. 27
• Time: 3:30 p.m. EST
• Venue: Vaught-Hemingway Stadium
• How to Watch (TV): ABC
• LSU record: 4-0
• Ole Miss record: 4-0 

LSU vs. Ole Miss Key Player to Watch

Garrett Nussmeier, Quarterback, LSU

A potential No. 1 overall pick in the 2026 NFL Draft, Nussmeier has gotten off to a decent start in the 2025 season, completing 68.6 percent of his passes for 962 yards, six scores and two picks.

He’s currently +2000 to win the Heisman in the 2025 season, but he’ll need to put up some more counting numbers to get that done for the No. 4-ranked Tigers.

LSU’s wins against quality teams have been knocked down a bit since Clemson and Florida are both struggling, but Nussmeier has led the team to the No. 28 success rate on pass plays in the country. 

He’ll look to attack an Ole Miss defense that has allowed quarterbacks to complete just 49.2 percent of their throws in the 2025 season. 

LSU vs. Ole Miss Prediction and Pick

Ole Miss has played a bunch of high-scoring games in the 2025 season, but it has only cleared 55.5 points in two of them.

Meanwhile, the Tigers have been a defensive-oriented squad in 2025, ranking 26th in defensive EPA/Play and 42nd in defensive success rate. LSU has combined for 27. 30, 30 and 66 points in four games.

I think this game ends up going UNDER, especially with Ole Miss dealing with some quarterback injury issues. Chambliss has been great in place of Simmons, but this LSU defense is a step up in class, as it ranks 26th in the country in EPA/Pass (-0.21). 

On the offensive side for the Tigers, their run game has not gotten going, ranking 89th in the country in EPA/Rush while averaging just 3.7 yards per carry. Ole Miss has been beatable on the ground, allowing 5.1 yards per carry while ranking 123rd in EPA/Rush on defense. 

However, I’m not sold on the Tigers being able to take advantage.

LSU has really slowed things down and played low-scoring games against Power Four opponents this season. I expect a similar result on Saturday afternoon. 

Pick: UNDER 55.5 (-112 at DraftKings)

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Odds refresh periodically and are subject to change.

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