Throw in the matchup with the Tigers in the nationally televised Atlantic Coast Conference opener for both teams, and the Cardinals are especially motivated.
Coach Bobby Petrino has urged the Cardinals to look ahead instead of back on those frustrating losses.
''I thought they did a real nice job of understanding that we need to put it behind us,'' Petrino said earlier this week. ''We've had two good practices, so I'm excited about that.''
Now they just need to convert that enthusiasm into execution.
Offensively, mobile freshman quarterback Lamar Jackson had a promising beginning to his first start. But he eventually gave way to sophomore Kyle Bolin, who directed two fourth-quarter touchdown drives but couldn't complete the rally against the Cougars.
Petrino hasn't named a starter against the Tigers, but Louisville could also use better run production after gaining just 70 yards against Houston.
The Cardinals' defense also seeks redemption after yielding 462 yards to the Cougars. Bouncing back certainly won't be easy in a short week against a Clemson squad that has outscored its first two opponents by a combined 90-20 margin.
Petrino hopes that urgency snaps the Cardinals back into focus.
''We've got a lot of work to do,'' said Petrino, whose team aims to avenge last year's 23-17 road loss at Clemson in which a rally fell short after reaching the Tigers' 1.
''We're playing a real good team in Clemson; their defense doesn't look like they missed a beat,'' Petrino said. ''They're physical, their front seven is very, very good, their linebackers come downhill and tackle well, their corners like to play press man, so that's a challenge there.
''But I think we're looking forward to that.''
Some things to watch when No. 11 Clemson visits Louisville:
WHO'S THE QB? Jackson took over for an ineffective Reggie Bonnafon against Auburn before being relieved by Bolin against Houston, leaving things uncertain at QB against the Tigers. Whoever starts not only has to establish consistency but hand off better than against Houston, when the Cardinals lost two exchanges.
WATSON'S BACK: Clemson quarterback Deshaun Watson was a freshman on an unstoppable two-week run in 2014 when an injury against Louisville sidelined him for a month. Watson broke a bone in his right, throwing hand early against the Cardinals at Death Valley last year, needing surgery and about four weeks to recover. ''As weeks went by, months went by, everything happens for a reason,'' he said of the recovery and what-ifs. ''For me, it was just one of those things that kind of happened, something I couldn't control.''
WRAP `EM UP: The short turnaround after the loss to Houston didn't leave the Cardinals much time to correct tackling and assignment breakdowns that doomed them against the Cougars. Their hope is that a back-to-basics approach can translate into better results against Watson.
DEFENSIVE STRENGTH: A year after Clemson had the nation's top-ranked defense, it stands 19th at 255 yards allowed per game. That's a few yards ahead of last season's average but lags behind six other ACC schools including No. 1 Boston College (51.1 yards a game).
RANKED CHALLENGE: Louisville will face its second ranked opponent in the first three games for the first time since 1991. Overall the Cardinals are 15-43-1 against top-25 teams including 7-10 at home.
AP Sports Writer Pete Iacobelli in Clemson, South Carolina, and freelancer Josh Abner contributed to this report.