Senior Jase Franke went down with a right knee injury during the first quarter of Saturday's 31-20 loss to Southern California at the Los Angeles Coliseum.
CU will find out the extent of the injury on Sunday, but it is feared to be a season-ending ACL tear.
Throughout his career, Franke, who is from nearby Camarillo, Calif., has been a key part of the rotation up front.
"He's meant a ton," head coach Mike MacIntyre said. "This is really, really tough. This is his home area. Everybody in the family was here tonight. It's a gut-wrenching loss for him and for our team. He's such a great leader, he's a good player."
Franke has 12 tackles and two sacks in the first five games. If he is out for the year, MacIntyre said, "We're going to miss Jace a lot."
It was a rough night overall for CU.
Senior receiver Jay MacIntyre left the game with a concussion, sophomore receiver Laviska Shenault injured a toe and running back Travon McMillian went out a thigh bruise, coach MacIntyre said.
Stuffing the run
CU's run defense was a bright spot, as the Trojans were limited to 62 yards on 27 carries.
"I was pleased with the way our defensive front played, our front seven," coach MacIntyre said. "I thought the front seven played really well and physical."
USC had gained at least 129 yards on the ground in each of the previous five meetings with the Buffs.
The Buffs didn't fare much better, with 95 yards on the ground. Most of those came on Shenault's 49-yard touchdown run. CU gained 46 yards on its other 36 carries.
With 3 minutes, 23 seconds to play, CU quarterback Steven Montez scored on a 19-yard touchdown run to pull the Buffs within 31-20. CU then went for a two-point conversion - and missed it.
It was a head-scratching decision to go for two in that situation, but the Buffs actually didn't know they were going for two.
Referees didn't clearly signal a touchdown on Montez's run and the stadium scoreboard didn't change. The Buffs - and those in the press box - thought they were lining up for a first-and-goal play at the 3-yard line, and Montez tossed an interception.
It wasn't until after the failed conversion that CU realized what happened.
"It was confusing to all of us," MacIntyre said. "We got totally screwed up on that, and I'll take complete responsibility for that. That's something I have to make sure I stop and ask or whatever. It was a confusing situation, but that's my fault.
Milestone for Shenault
Shenault had nine catches, giving him 60 for the season. It's just the 10th 60-catch season in CU history - and he's only halfway through the season.
Saturday was the first time this season that Shenault failed to score on an receiving touchdown. He did get in the end zone a 49-yard run, however.
Following that Montez touchdown, the Buffs' Kyle Trego recovered the ensuring onsides kick. It was the first successful onsides kick by the Buffs since 2014. Redshirt freshman receiver Jaylon Jackson made his CU debut and caught his first two career passes, for 19 yards. Freshman cornerback Chris Miller made his first career start. Senior linebacker Drew Lewis had his first career interception, and senior Evan Worthington had his fourth career interception. CU has yet to allow a fourth quarter touchdown this season. Montez, who came into the game completing 75 percent of his passes, completed just one of his last 10 throws.
Contact staff writer Brian Howell at firstname.lastname@example.org or twitter.com/BrianHowell33.