The 19th-ranked Cardinals look to bounce back from their first loss in a month and continue their dominance over the lowly Blue Demons, who are mired in a 36-game losing streak to Top 25 teams.
Louisville (20-6, 8-5 Big East) seemed poised to upset No. 2 Syracuse on Monday, leading by five with 3:38 remaining, but the Orange would score the game's final six points and hand the Cardinals a 52-51 loss.
"There are no moral victories," Pitino said. "We are crushed with this loss - absolutely crushed. We didn't get the job done when we should have. The only thing that will erase this loss is to beat them up there."
While winning at the Carrier Dome on March 3 will be a tall order for Pitino's team, it shouldn't have trouble earning a victory at Allstate Arena.
The Cardinals defeated the Blue Demons 76-59 at home on Jan. 14 and have won 21 of the last 23 meetings. They've won eight straight in the series since a 60-58 overtime loss in 2004, when both teams were in Conference USA.
DePaul (11-14, 2-11), in 15th place in the 16-team Big East, has lost 36 straight to ranked opponents since an 84-76 victory over then-No. 17 Villanova on Jan. 3, 2008.
A major reason for the Blue Demons' struggles is their defense allowing 76.2 points per game, worst of the 74 schools in the six BCS conferences. Facing a DePaul defense surrendering an average of 82.8 points on 50.7 percent shooting during a five-game losing streak could be just what Louisville needs after being stymied by Syracuse's zone.
Against the Orange, the Cardinals shot 34.7 percent, including 5 of 19 from beyond the arc, to finish with their lowest scoring output of the season. They averaged 75.3 points in winning their previous six games.
Freshman Chane Behanan led the way against Syracuse with 16 points on 7-of-8 shooting, but senior Kyle Kuric, who averages a team-best 12.8 points, scored three and went 1 for 8 from the field.
Russ Smith and Chris Smith, who combine to average 22.4 points, totaled 13 points on 3-of-15 shooting Monday but had no problems hitting shots against DePaul last month.
Russ Smith scored 25 while Chris Smith added 20 points and made four 3-pointers for the Cardinals, who shot 50.9 percent and outrebounded the Blue Demons 41-33.
Louisville also did a good job of shutting down Cleveland Melvin, limiting the conference's third-leading scorer to eight points on 3-of-11-shooting.
Melvin, who averages 17.8 points, had another tough night in Wednesday's 80-54 loss to Connecticut, DePaul's 10th defeat in 11 games. The 6-foot-8 sophomore missed 9 of 14 shots to finish with 11 points.
"When he got the ball there were three guys eyeballing him, if not four," coach Oliver Purnell said. "That's happening now and it's going to continue to happen."
The lack of other good scoring threats has plagued Melvin and the Blue Demons. Second-leading scorer Brandon Young has been struggling, averaging 8.0 points on 27.6 percent shooting over his last seven games.
Young was the only DePaul player to score in double figures in the first matchup against Louisville with 14 points, but he was 5 for 16 from the field as the team shot 34.3 percent.
The Cardinals lead the Big East in field-goal percentage defense at 37.1.
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