Louisville vs. Michigan State odds, prediction: 2026 NCAA Tournament picks from proven model

The sixth-seeded Louisville Cardinals face the third-seeded Michigan State Spartans in the second round of the NCAA Tournament East Region on Saturday. Louisville advanced by slipping past South Florida 83-79 in the first round on Thursday, while Michigan State dropped North Dakota State 92-67. The Cardinals (24-10), who placed sixth in the Atlantic Coast Conference at 11-7, are 3-6 against ranked teams this season. The Spartans (26-7), who tied for second in the Big Ten Conference standings at 15-5, are 5-4 against ranked foes this year.

Tipoff from KeyBank Center in Buffalo, N.Y., is set for 2:45 p.m. ET. Michigan State is a 4.5-point favorite in the latest Louisville vs. Michigan State odds, while the over/under for total points scored is 151.5. 

Before making any Louisville vs. Michigan State picks, you NEED to see the basketball predictions from the SportsLine Projection Model.

The SportsLine Projection Model simulates every college basketball game 10,000 times. It entered the 2026 NCAA Tournament on a sizzling 11-1 run on top-ranked over/under picks dating back to last year, and is on a 28-22 run on top-rated CBB side picks. Anyone following could have seen HUGE returns!

The model has simulated Louisville vs. Michigan State 10,000 times and the results are in. The model is going Over on the total, and it also says one side of the spread hits almost 70% of the time!

So who wins Louisville vs. Michigan State, and which side of the spread hits almost 70% of the time? Join SportsLine right now to see which side of the spread you need to jump on, all from the computer model that has simulated this matchup 10,000 times!