South Florida vs. Louisville Prediction, Odds, Best Prop Bet for NCAA Tournament 1st Round

Thursday’s NCAA Tournament action kicks off at 12:15 p.m. EST, and shortly after the No. 11 South Florida Bulls will take on the No. 6 Louisville Cardinals.

The Bulls won the American Athletic Conference this season, clinching a spot in the NCAA Tournament, and they have a dynamic scoring guard in Wes Enis that believes his team can make a run in the tournament.

"Yeah, I don't think it's an upset. I think we're the better team. I don't really care what 11-6 says."

USF Guard Wes Enis when asked what a win over Louisville would mean to him in March Madness.pic.twitter.com/6URsmVqNjI
— Underdog (@Underdog) March 17, 2026

Louisville earned an at-large bid after a solid season in the ACC, but the status of guard Mike Brown Jr. (out, back) looms large after he did not play in the ACC Tournament. Brown will miss the entire opening weekend of the NCAA Tournament.

Breaking: Louisville will be without star freshman Mikel Brown Jr. in the opening weekend of the NCAA tournament, the school announced.

He's been dealing with a back injury and will not play against No. 11 South Florida and will also not play if Louisville advances. pic.twitter.com/Dgpb3IwRK2
— ESPN (@espn) March 18, 2026

Oddsmakers have set the Cardinals as favorites in this matchup, but should bettors trust them to cover?

Here’s a look at the betting odds, a player prop to consider and my prediction for this first-round matchup.

South Florida vs. Louisville Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

South Florida +4.5 (-112)
Louisville -4.5 (-108)

Moneyline

South Florida: +170
Louisville: -205

Total

164.5 (Over -110/Under -110)

South Florida vs. Louisville How to Watch

Date: Thursday, March 19
Time: 1:30 p.m. EST
Venue: KeyBank Center
How to Watch (TV): TNT
South Florida record: 25-8
Louisville record: 23-10

South Florida vs. Louisville Best Prop Bet

Izaiyah Nelson 8+ Rebounds (-130)

Senior big man Izaiyah Nelson has been a beast on the glass this season, averaging 9.6 rebounds per game for the Bulls. He’s picked up at least eight boards in 23 of his 33 games this season.

Louisville does a nice job on the defensive glass (31st in defensive rebound rate), but it’s just 94th in the country in offensive rebound rate. I still think that sets up well for Nelson, who is averaging 5.7 defensive rebounds and 3.9 offensive rebounds per game.

Against NCAA Tournament teams, Nelson has put together some big rebounding games. He had 12 boards against VCU, 12 boards against Alabama, 10 boards against Utah State and 11 boards against UMBC.

The Bulls are the No. 6 team in the country in offensive rebound rate, so they may be able to win the battle on the boards on Thursday.

South Florida vs. Louisville Prediction and Pick

Louisville star guard Mikel Brown Jr. is out for the first weekend of the NCAA Tournament after missing the ACC Tournament, and that makes South Florida an interesting potential upset pick in the first round of this tournament.

South Florida needed to win the AAC to get into the field, but the Bulls have an impressive defensive resume, ranking 40th in adjusted defensive efficiency, per KenPom. The Bulls are also:

47th in opponent effective field goal percentage
56th in opponent turnover rate
24th in opponent 2-point percentage.

South Florida also loves to push the pace, ranking 15th in KenPom’s adjusted tempo metric.

Louisville has a pretty strong profile, but the ACC wasn’t super deep this season, as shown by just two teams (Duke and Virginia) receiving better than a No. 6 seed in the tournament.

South Florida is a must-bet for me with Brown out.

Pick: South Florida +4.5 (-112 at DraftKings)

Odds refresh periodically and are subject to change.

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