The Titans and Colts met at LP Field on September 16. After a slow start from both offenses, the Colts struck first with an 8-yard run by Joseph Addai, but Colts kicker Adam Vinatieri missed the point after. With 1:03 left in the first quarter, the Titans scored with a 30-yard field goal by Rob Bironas. In the second quarter, the Colts scored another touchdown via a 22-yard touchdown pass from Peyton Manning to Dallas Clark. Both sides kicked another field goal in the quarter, and the Colts led 16-6 at the break. After the break, Adam Vinatieri made another field goal to extend the Colts' lead. Titans running back LenDale White scored a rushing touchdown, while Vinatieri's field goal attempt was tipped but bounced over the crossbar to end the third quarter. Vinatieri missed a 36-yard attempt early in the fourth quarter and Vince Young threw a 1-yard touchdown pass to Roydell Williams to end the game's scoring. With the Titans' 22-20 loss, the team fell to 1-1 on the season.

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