The Cardinals had an opportunity to win the game in regulation but Damion Lee's three-pointer at the buzzer rattled off.
Puerto Rico took a lead in overtime and never looked back as they won 102-94.
Lee led the Cardinals with 29 points and 10 rebounds. Jaylen Johnson and Ray Spalding each finished with 11 points.
Damion Lee is averaging 24.6 PPG during Louisville's first three games in Puerto Rico. Has evolved off the bounce. No longer just a shooter.— Jon Rothstein (@JonRothstein) August 14, 2015
Louisville is now 0-5 against Puerto Rico this week.
Here is a recap from UL:
Damion Lee led the Cardinals in scoring with 29 points and 10 rebounds. Jaylen Johnson and Raymond Spalding each finished with 11 points while Mangok Mathiang added 10 points. Angel Vassallo led Puerto Rico with 29 points.
The Cardinals led Puerto Rico through three quarters. Puerto Rico fought back from 12 points down and cut the Louisville lead to five in the fourth quarter. At the 1:39 mark, the Cardinals held a four point lead (85-81). Puerto Rico tied the game at 87 and had a chance for the win but Quentin Snider stole the ball. Lee had missed a three-pointer at the end of regulation, forcing the overtime period.
"The guys (Louisville) played great tonight," said UofL Coach Rick Pitino, who did not coach either team while observing both. "This was by far our best performance. All of our bigs played terrific, but just got in foul trouble. Down the stretch we had no interior shot blocking when they were out and Puerto Rico took advantage of mismatches."
Assistant coach Ralph Willard guided the Cardinals while Pitino observed the exhibition game. Pitino is coaching the Puerto Ricans in two international events this summer, including the 10-team, 2015 FIBA Americas Championship in Mexico City, Mexico on Aug. 31-Sept. 12, where the top two teams qualify for the 2016 Olympic Games in Rio de Janeiro, Brazil. "I was trying to observe Puerto Rico tonight because we have to make a cut, and I wanted to watch Louisville without trying to beat them," said Pitino.
"This is a great group," said Pitino about the Cardinals. "It's a very special group. I have a great feeling about these guys and what they're all about. Tonight, a veteran team beat them mentally. They took advantage of switches. The last few nights, (Louisville) has been penetrating to get their shots. Tonight, they penetrated to get somebody else a shot. That was a point of emphasis and we had terrific passing."
Puerto Rico took control early in the overtime period with a 96-90 lead. The Cardinals were never able to regain the lead before falling 102-94. Louisville shot the ball well, connecting on 57 percent from the field and 43 percent from behind the arc. Sophomore Chinanu Onuaku sat out the game but is expected to play with the Cardinals on Friday.