Louisville vs. Michigan State odds, March Madness predictions: 2026 NCAA Tournament picks from proven model

SportsLine's model simulated Michigan State Spartans vs. Louisville Cardinals and revealed its college basketball picks for this NCAA Tournament 2026 second-round matchup on Saturday

The sixth-seeded Louisville Cardinals face the third-seeded Michigan State Spartans in the second round of the 2026 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 ACC at 11-7, are 3-6 against ranked teams this season. The Spartans (26-7), who tied for second in the Big Ten 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 on CBS. The Spartans are 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, check out the Louisville vs. Michigan State 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 its top-rated over/under college basketball picks dating back to last season, and is on a 28-22 run on top-rated CBB side picks. 

Now, the model has simulated Louisville vs. Michigan State 10,000 times and just revealed its college basketball picks and predictions. You can head to SportsLine now to see the model's picks. Here are several college basketball odds and college basketball lines for Michigan State vs. Louisville:

Louisville vs. Michigan State spread:    

Michigan State -4.5

Louisville vs. Michigan State over/under:    

151.5 points

Louisville vs. Michigan State money line:    

Michigan State -217, Louisville +178

Louisville vs. Michigan State picks:    

Louisville vs. Michigan State TV:

CBS

Top Louisville vs. Michigan State predictions

After 10,000 simulations of Louisville vs. Michigan State, SportsLine's model is going Over on the total (151.5 points). The Over has hit in four of their last six head-to-head meetings. The Over also hit in Louisville's last game. The Over has hit in eight of the last 10 Michigan State games, including each of the last four.

The model projects the Cardinals to have three players score 12 points or more, including Ryan Conwell, who is projected to score 19.3 points. The Spartans are projected to have four players score 11.2 points or more, led by Jeremy Fears Jr., who is projected to score 15 points. The model is projecting 152 combined points as the Over hits 51% of the time  You can get the spread pick at SportsLine.

How to make Michigan State vs. Louisville picks

Now, the model simulated every possession of Michigan State vs. Louisville 10,000 times and says one side of the spread hits in almost 70% of simulations. You can only see that pick at SportsLine.

So who wins Louisville vs. Michigan State, and which side of the spread hits almost 70% of the time? Visit SportsLine now to see which side of the Louisville vs. Michigan State spread to back, all from the advanced model that just simulated this game 10,000 times, and find out.