Freeney was out of practice all week with an abdomen injury for the Colts, who have won 19 consecutive regular-season games.
With Freeney out, the Colts are likely to start versatile defensive lineman Raheem Brock in Freeney's spot. Brock has played end and tackle.
Indy (10-0) can clinch the AFC South title with a win and a Jacksonville loss.
The Associated Press contributed to this report