Junior quarterback Peyton Ramsey got the start for Indiana and went 19 for 33 for 162 yards with zero touchdowns and an interception. He was also sacked four times -- the first sacks allowed by the Hoosiers this season.
On Thursday, coach Tom Allen said Penix was "working through some things right now" but gave no specifics.
Allen said he wasn't aware of Penix, a freshman, being injured in last week's 52-0 win over Eastern Illinois.
Penix has thrown for 523 yards with three touchdowns and two interceptions during the Hoosiers' 2-0 start.
The Associated Press contributed to this report.