Lee was injured around midfield after he was tackled following an 18-yard punt return early in the fourth quarter while USC was down 48-21. Lee laid down on the field for several minutes after the play before being carried off the field by two teammates to the team's training table.
"Obviously it didn't look very good," Trojans coach Lane Kiffin said after the game. "It didn't sound very good or look very good, so that's all I got for you."
While USC's medical staff looked at Lee's left knee, several teammates came by to check on Lee as he hid his face under a towel. Lee was later carted back to the locker room.
Before his injury, Lee became USC's all-time receiving yards leader with 3,238 yards. He had seven catches for 92 yards in the game.
Lee was not available for comment after the game but a team official said Lee left the locker room on crutches and would get tests done in Los Angeles.
Lee, who figures to be picked high in the NFL draft, has loss of value insurance should he slip significantly in the draft. He also has a $10 million total disability policy, but would have to never play football again to collect that sum.
ESPN.com's Darren Rovell contributed to this report.