The No. 6 Louisville Cardinals play the No. 3 Michigan State Spartans in the second round of the NCAA Tournament from Buffalo, New York. Tip-off is set for 2:45 p.m. ET on CBS.
Michigan State is favored by 5.5 points on the spread with a moneyline of -225. Meanwhile, Louisville is the underdog at +5.5 with a moneyline of +185. The total is set at 151.5 points.
Here's my Louisville vs. Michigan State prediction and college basketball picks for March 21, 2026.
Louisville Cardinals vs Michigan State Spartans Prediction, Picks
My Pick: Michigan State -4.5 (Play to -6)
My Louisville vs Michigan State best bet is on the Spartans to cover the spread. For all of your college basketball bets, be sure to find the best lines by using our live NCAAB odds page.
Louisville vs Michigan State Odds, Point Spread, Line
| Louisville Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+4.5 -110 | 151.5 -115o / -105u | +170 |
| Michigan State Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-4.5 -110 | 151.5 -115o / -105u | -210 |
- Louisville vs Michigan State Spread: Michigan State -4.5, Louisville +4.5
- Louisville vs Michigan State Over/Under: 151.5
- Louisville vs Michigan State Moneyline: Louisville ML +170, Michigan State ML -210
Louisville vs Michigan State NCAA Tournament Pick, Preview
Louisville held on for dear life against South Florida, but it failed to cover 4.5 points due to some flimsy late ball-handling.
The Cardinals went a scalding 13-for-25 from deep, but held USF to 5-for-33 (finally variance in Louisville's favor).
Shooting will determine if Louisville can beat Tom Izzo in March. Pat Kelsey is a more modern coach, as Louisville sits at 60th in adjusted tempo. The Cardinals also shoot 3s at a 52.7% rate and hit 36% of them.
Kelsey relies on a sharp backcourt, featuring Ryan Conwell and Isaac McKneely. That pair went off when Louisville needed it most due to Mikel Brown Jr. being out due to a back issue. Conwell scored 16+ points in five of his past six games, and McKneely went 7-for-10 from 3 in the win over USF.
I'll give credit where it belongs. Louisville isn't just a shooting team; it also ranks 25th in defensive efficiency. The Cardinals are smaller than Michigan State, but they make up for it by limiting teams to 48% shooting from 2-point range and 32% from 3.
Keep an eye on Sananda Fru. Fru is coming off the bench in place of Vangelis Zougris, but Fru plays the most important minutes. The 6-foot-10 big man leads Louisville with a 7% block rate and 14% offensive rebound rate.
Adrian Wooley also has to play better than he did on Thursday. He scored four points with three turnovers and one assist. It was fine against South Florida; it won't be against Michigan State.
Meanwhile, Michigan State hammered North Dakota State in the Round of 64 and covered the 16.5-point spread.
This is your prototypical Tom Izzo team, with the Spartans ranking 13th in defensive efficiency per KenPom. And I expect one of the top coaches in college basketball history to create a plan to limit Louisville's shooting.
For one, the Spartans play such tight defense that it forces teams to play late in the clock, even if they don't plan to. On average, Michigan State chops 18 seconds off the clock on defense, and teams shoot 3s 45% of the time against it.
Another Izzo staple is rebounding. This is one of his better rebounding squads, limiting teams to a 22% offensive rebound rate (the lowest nationally). On the other end, Michigan State grabs its misses 38% of the time — one of the top splits in the country, and it leads to it winning the shot-volume battle in most games.
On the offensive end, the Spartans will look to dominate Louisville on the boards, just like USF did. The Bulls snagged 18 offensive rebounds, and Michigan State could take advantage there.
The point guard disparity is scary for the underdogs. Jeremy Fears Jr. is one of the top lead guards in America, leading MSU with 15.4 point and a nation-leading 9.2 assists while turning it over 2.3 times per game.
I wouldn't call Michigan State a "good" shooting team. On a percentage basis, the Spartans shoot 36% from 3 — a very strong number. However, they take 3s just 36% of the time. I feel better about their shooting now, as Jordan Scott emerged as a real weapon.
Scott, Kur Teng and Jaxon Kohler each shoot close to 40% from 3. Having a lineup with three shooters when Izzo takes Coen Carr off the floor gives them a bit more versatility.
I'm laying the points with Michigan State. Sure, Louisville played well enough against South Florida, but having to battle the size of Kohler and Carson Cooper with the point guard play of Fears will make this a tough game for the Cardinals.
My Pick: Michigan State -4.5 (Play to -6)
