LSU vs. Ole Miss prediction, odds, line, time: 2025 college football Week 5 picks from proven computer

A top-15 SEC matchup is on tap for Saturday as Brian Kelley and the No. 4 LSU Tigers will visit Lane Kiffin and the No. 13 Ole Miss Rebels. LSU (4-0, 1-0), finally flexed its muscle on offense with a 56-10 win over Southeastern Louisiana last week after being held to 23 points or fewer in each of its first three games. Ole Miss (4-0, 2-0) easily handled Tulane, 45-10, in Week 4 after back-to-back conference victories over Kentucky and Arkansas. The home team has won five straight and 11 of 13 in this series.

Kickoff is at 3:30 p.m. ET from Vaught-Hemingway Stadium in Oxford, Miss. LSU defeated Ole Miss, 29-26, in overtime last season. The Rebels are 2-point favorites in the latest LSU vs. Ole Miss odds, while the over/under for total points is 57.5. Before making any Ole Miss vs. LSU picks, check out the college football predictions from the SportsLine Projection Model. 

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The model simulates every FBS game 10,000 times. Since its inception, it has generated a betting profit of well over $2,000 for $100 players on its top-rated college spread football picks, and is a profitable 35-22 combined on money-line and over/under college football picks since the beginning of 2024. Anybody following its college football betting picks at sportsbooks and on betting sites could have seen strong returns.  

Now, the model has set its sights on Ole Miss vs. LSU. You can visit SportsLine now to see the picks. Here are the FBS college football odds and trends for LSU vs. Ole Miss:

Why LSU can cover

The Tigers are coming off a 46-point over SE Louisiana, but don’t expect a letdown in the team’s first SEC road game. LSU is 6-1 both straight-up and against the spread (ATS) following a 40-point win over the last 10 years. All seven of those games were against teams currently in the SEC, so LSU wasn’t simply dominating inferior opponents. Additionally, LSU will be visiting an Ole Miss squad which has often come up short when favored in big games as the Rebels are just 1-6 ATS over their last seven contests as favorites versus ranked teams.

LSU’s defense has been among the best in the nation, holding opponents to just 9.2 points per game, which is the ninth-fewest in FBS. No opponent has scored more than 10 points versus LSU nor reached even 90 yards on the ground. On offense, quarterback Garrett Nussmeier kept his name alive in the Heisman conversation with his performance in his last game. He had 273 yards and three touchdowns thru the air while also rushing for a score. He posted a career high in completion percentage as LSU should have a balanced offensive attack versus a Rebels squad which ranks last in the SEC in run defense. See which team to back at SportsLine. 

Why Ole Miss can cover

Being in Oxford is certainly an advantage for Ole Miss, as not only has the home team prevailed in each of the last five meetings between these teams, but the home squad has covered in seven straight matchups. Ole Miss has covered in all three of its home games this season and has been on quite a run at Vaught-Hemingway Stadium for a while. The Rebels have won in six straight home games, dating back to last season, and Lane Kiffin’s crew has prevailed in 16 of its last 17 home games overall.

As is the case with most Kiffin-coached teams, these Rebels are elite offensively, ranking among the top dozen FBS team in points per game (44.8), yards per game (544.8) and yards per play (7.4), even as they’ve played both Austin Simmons and Trinidad Chambliss at quarterback. The team has at least three rushing touchdowns in every game, while the Rebels’ pass defense is also a strength of the team. Ole Miss has held three of four opponents under both 200 passing yards and a 50% completion rate. See which team to back at SportsLine.

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How to make LSU vs. Ole Miss picks

SportsLine’s model has simulated Ole Miss vs. LSU 10,000 times and is going Over on the total, projecting 58 combined points. It also says one side of the spread hits in well over 60% of simulations. You can only get the pick at SportsLine. 

So who wins LSU vs. Ole Miss, and which side of the spread hits well over 60% of the time? Visit SportsLine now to see which side of the Ole Miss vs. LSU spread to jump on, all from the advanced model that is up over $2,000 on its FBS college football picks since its inception, and find out.