No. 3 Michigan State vs No. 6 Louisville NCAA Tournament Second Round predictions: Odds, trends and best bets

The second round of the East Region of the NCAA Tournament begins Saturday with No. 3 Michigan State taking the court against No. 6 Louisville.

The third-seeded Michigan State Spartans and sixth-seeded Louisville Cardinals meet Saturday in Buffalo in the second round of the 2026 NCAA. Both teams acquitted themselves nicely in the First Round. The Spartans cruised to a 92–67 victory over North Dakota State, while the Cardinals led basically start to finish and eventually secured an 83–79 win against South Florida.

Michigan State’s size is an obvious advantage. Sparty undoubtedly will look to exploit its advantage on the glass, led by 6'10" senior Jaxon Kohler , who averages 9.1 rebounds and 12.7 points per game. No surprise but the Spartans are one of the nation's most physical teams, ranking third in rebounding margin (+11). They face a Louisville squad takes the court again without their sensational freshman guard Mikel Brown Jr. , who was averaging 18.2 points before being sidelined with back issues. Without Brown and his ability to get to the rim, the Cardinals will rely heavily on Ryan Conwell and their perimeter offense to combat the aforementioned Michigan State size advantage.

These schools have met in the NCAA Tournament previously. The most notable was the Spartans' overtime win against the Cardinals in the 2015 Elite Eight.

Lets take a closer look at tonight’s matchup and take into consideration lineups, injuries, and other factors affecting the line and total.

We’ve got all the info and analysis you need to know ahead of the game, including the latest info on how to catch tipoff, odds courtesy of DraftKings recent team performance, player stats, and of course, our predictions, picks best bets for the game from our modeling tools and staff of experts.

Game Details and How to Watch Live: Michigan State vs. Louisville

• Date: Saturday, March 21, 2026

• Time: 2:45PM EST

• Site: KeyBank Center

• City: Buffalo, NY

• Network/Streaming: CBS

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Game Odds: Michigan State vs. Louisville

The latest odds as of Friday courtesy of DraftKings :

• Moneyline: Michigan State Spartans (-185) vs. Louisville Cardinals (+154)

• Spread: Michigan State -4.5

• Total: 151.5 points

This game opened Michigan State -4.5 with the Total set at 150.5.

Be sure to check out DraftKings for all the latest game odds & player props for every matchup this week on the NCAA Basketball schedule!

Expected Starting Lineups: Michigan State vs. Louisville

Michigan State Spartans

• G Jeremy Fears Jr.

• G Carson Cooper

• F Jordan Scott

• F Jaxon Kohler

• F Coen Carr

Louisville Cardinals

• G J’Vonne Hadley

• G Isaac McKneely

• G Adrian Wooley

• G Ryan Conwell

• F Vangelis Zougris

Important stats, trends and insights: Michigan State vs. Louisville

• Michigan State is 17-15 ATS overall this season

• Louisville is 16-18 ATS overall this season

• The OVER has cashed in 14 of Louisville’s 34 games this season (14-20)

• The OVER has cashed in 16 of Michigan State’s 33 games this season (16-17)

• Carson Cooper scored 20 points and pulled down 10 boards in Round 1 for Sparty

• Isaac McKneely was 7-10 from 3-point range in Round 1 against South Florida

Rotoworld Best Bet

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Our model calculates projections around each moneyline, spread and over/under bet for every game on the NCAA calendar based on data points like recent performance, head-to-head player matchups, trends information and projected game totals.

Once the model is finished running, we put its projections next to the latest betting lines for the game to arrive at a relative confidence level for each wager.

Here are the best bets our model is projecting for Saturday’s game between Michigan State and Louisville:

• Moneyline: Rotoworld Bet is recommending a play on Michigan State on the Moneyline

• Spread: Rotoworld Bet is recommending a play on Michigan State -4.5

• Total: Rotoworld Bet is leaning towards a play on the Game Total OVER 151.5

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