Louisville guard Reyne Smith tried to play through injury, but his right ankle gave way in the second half as the Cardinals' season came to an end with an 89-75 loss to Creighton on Thursday.
Smith collapsed into a fetal position with 11:37 left in the Cardinals' first-round game. He had missed Louisville's past four games due to the injury, sitting out the regular-season finale and all three games at the ACC tournament, including the team's first appearance in the title game.
With Smith curled up on the court and visibly upset across from the Louisville bench, his teammates hugged each other while surrounding him. First-year coach Pat Kelsey knelt over Smith before signaling for a towel.
Smith put the towel over his head then was helped off the court, barely able to put any weight on his right foot.
The senior from Australia started and played 20 minutes before aggravating his injured ankle. He left with five points.
Cardinals swingman Terrence Edwards Jr. said Smith worked diligently to recover in time for Louisville's first March Madness appearance since 2019.
"Our heart goes out to Reyne," Edwards said. "We knew he wasn't 100 percent, but what he did today is something I'll remember forever. He sacrificed his body and put his body on the line tonight for us, so we could try to come out with the win. He knew how much we needed him.
"I'm just so proud of him, and he'll get back right for sure. What he did for us today is something that will go a long way outside of basketball."
The win was Creighton's fifth straight in the NCAA tournament first round. Jamiya Neal scored a career-high 29 points and had 12 rebounds, while Steven Ashworth connected from well beyond the arc on the way to 22 points.
Seeking its fourth Sweet 16 appearance in five years, Creighton (25-10) will play either No. 1 overall seed Auburn or 16th-seeded Alabama State in the second round of the South Region on Saturday.
Chucky Hepburn scored 22 points and Terrence Edwards Jr. had 21 for Louisville (27-8), which improved its record by 19 wins over last season with a transfer-heavy roster. It was the Cardinals' first March Madness appearance since 2019.
The Associated Press contributed to this report.