The men's basketball matchup marked Houston's first visit to Oklahoma since Dec. 17, 2011.
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In the first half, the Cougars shot 67% and outscored the Sooners.
Houston forward J'Wan Roberts left the game with 2:27 minutes left in the first half with an apparent finger injury, but returned to the game in the second half after receiving stitches in his right hand.
UH led the way over OU, 48-45, at the half. There were a total of 17 lead changes and 10 ties in the first half of the game.
UH guard L.J. Cryer scored a team-high 23 points, while backcourt teammate Jamal Shead finished with 14 points and dished out six assists.
As for Oklahoma, guard Rivaldo Soares recorded a team-high 23 points along with four rebounds.
UH's Shead sealed the game with a game-winning bucket late, with 0.1 seconds left in the game.
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After Saturday's win over OU, Houston improved to an overall record of 26-3 in the season and continues to sit atop the nation in the latest Associated Press Top 25 poll.
Houston looks to wrap up their road trip when the team faces Central Florida on Wednesday.
Remaining UH schedule
- March 6: at UCF, airs on ESPN+
- March 9: Kansas, airs on ESPN