The first round of the NCAA Tournament begins on Thursday, March 19, featuring a first-round clash between the No. 6 Louisville Cardinals (23-10) and No. 11 South Florida Bulls (25-8).
Fresh off an 11-game win streak, the Bulls eye an upset against a seasoned Cardinals squad favored by 3.5 points on PrizePicks Team Picks.
Let’s break down our South Florida vs. Louisville spread prediction for this NCAA Tournament showdown, tipping at 1:30 p.m. ET on TNT. Make your college basketball picks on PrizePicks and PrizePicks Team Picks and earn real money if you’re right, including on game winners, spreads, and totals!
New users on PrizePicks can start the 2026 NCAA Tournament with $50 in Lineups instantly after playing $5+ — win or lose! Just sign up with promo code PLAYBOOK and you’re good to go.
{{nba_offer_banner="/style-system/ui-components-playbook"}}
South Florida vs. Louisville Prediction, Spread, Over/Under
The Cardinals are a trendy pick to make a deep second-weekend run in the 2026 NCAA Tournament. Louisville battled its way to a 23-10 record in a grueling ACC, relying on an elite perimeter attack that averages 84.8 points per game.
South Florida has overwhelmed opponents with a top-10 offense that averages a staggering 87.0 PPG. G Wes Enis is one of the most polarizing mid-major players, leading the Bulls with 16.8 PPG and earning AAC Tournament Most Outstanding Player honors. He's complemented by F Izaiyah Nelson (9.6 RPG).
Louisville has heavily dominated South Florida in its history, holding a 29-4 all-time series lead. The Cardinals came away with an 80-54 win at the KFC Yum! Center in their last meeting back in 2014.
However, covering the 3.5-point spread against this scorching-hot Bulls squad may be a massive test for head coach Pat Kelsey's defense.
South Florida vs. Louisville Spread, Over/Under
The Bulls enter this matchup as 3.5-point underdogs, returning a 2.56x payout on PrizePicks Team Picks if South Florida wins outright.
Meanwhile, Louisville is the favorite with a 1.47x payout with a win, via PrizePicks Team Picks, where you can earn money with your picks in 35 states.
- Spread: Louisville Cardinals -3.5 (1.78x payout)
- Over/Under: 162.5 (1.75x payout on over)
- Game Winner Payout: South Florida 2.56x | Louisville 1.47x
Team Picks data is live as of writing and is subject to change.
🔥 Get College Basketball Predictions and Picks from the experts for the NCAA Tournament
South Florida vs. Louisville Prediction on Spread – 3/19/26
Here are some key stats to know before locking in your South Florida vs. Louisville prediction against the spread for the NCAA Tournament matchup on Thursday, March 19, on PrizePicks.
- South Florida owns an 18-14 against-the-spread record, while Louisville sits at just 15-18 ATS.
- According to Bart Torvik, Louisville carries an adjusted offensive efficiency of 118.0 (28th nationally), but that number is inflated by inferior opposition. The Cardinals converted just 24% from deep in the ACC Tournament and shoot 33.4% from beyond the arc in Quad 1 matchups.
- South Florida scores 87.0 PPG and allows just 75.5 PPG, producing a +12.2 averaging margin — one of the stronger differentials among mid-major programs in the field.
- Louisville's leading scorer, G Ryan Conwell, is averaging 18.7 PPG while shooting 34.2% from deep. Star freshman G Mikel Brown Jr. is confirmed out for the first two rounds due to a back injury, and the Cardinals score 8.8 fewer PPG over their last four without him.
- South Florida's aggressive frontcourt, led by Nelson, could be a tough matchup for G J'Vonne Hadley, who's stepped up as Louisville's secondary engine in the last four games (15.8 PPG, 4.3 RPG).
- Enis averages 16.8 PPG and has knocked down 36.5% of his 3-point attempts, giving the Bulls a reliable scoring option on the perimeter to keep pace with Louisville's high-volume 3-point attack (11.5 makes per game, fifth nationally).
- Louisville attempts 32.3 3-pointers each night (third in the country), but South Florida's opponents are shooting just 33.9% from deep against them.
{{nba_offer_banner="/style-system/ui-components-playbook"}}
Make South Florida vs. Louisville Picks on PrizePicks
South Florida has been an absolute buzzsaw down the stretch of the 2025-26 campaign, capping off a dominant run with an AAC crown. Can the Bulls channel that scorching momentum into a massive first-round upset as the NCAA Tournament officially gets underway?
You can make your South Florida vs. Louisville picks on PrizePicks and PrizePicks Team Picks to earn real money. Just pick players, predict More or Less on their projected stats, and cash in if you’re correct. With Team Picks, make predictions on winners, spreads, and over/unders, now available in 35 states.
Check out the Playbook throughout the 2026 NCAA Tournament for more college basketball predictions, picks, and news every day.
