Indianapolis linebacker D'Qwell Jackson has been suspended four games for violating the NFL's policy on performance-enhancing substances.
With FS Mike Adams (groin) out, CB Darius Butler filled-in at safety in Week 9 against Green Bay.
The Indianapolis defense has just eight sacks through six weeks, good for 28th in the NFL.
Jacksonville QB Blake Bortles threw for 548 yards and four touchdowns in two 2015 meetings with Indianapolis.
The Indianapolis secondary will be without cornerbacks Darius Butler and Vontae Davis in Week 1, who are both out with ankle injuries.
The Indianapolis defense will face struggling Tennessee quarterback Zach Mettenberger in Week 17.
In Week 16, the Indianapolis defense will face the slumping Miami offense that has averaged just 271.2 total yards in the last five weeks.
The Indianapolis defense has allowed an astonishing 96 points over the last two weeks.
The Indianapolis Colts travel to Pittsburgh in Week 13 to face the Steelers, who are fourth among NFL offenses in total yardage.
Indianapolis' 29th-ranked pass defense will take on Tampa Bay rookie QB Jameis Winston in Week 12.
The Indianapolis Colts will enjoy a bye in Week 10 but face the Atlanta Falcons in Week 11, who are fifth among NFL offenses with an average of 402.2 total yards per game.
The Indianapolis defense is 28th among NFL teams in run defense, allowing 124.9 yards per game this season.
The Indianapolis Colts travel to Carolina on Monday to face the Panthers and the NFL's leading rushing attack.
The Indianapolis Colts are 29th in total defense this season, allowing 401.8 total yards per game.