Coming off their last-second road win over the Vikings, the Colts went home for a Week 3 AFC South duel with the Jacksonville Jaguars. In the first quarter, Indy was first out of the gates as QB Peyton Manning completed a 4-yard TD pass to WR Marvin Harrison. In the second quarter, the Jaguars took the lead with kicker Josh Scobee getting a 26-yard field goal, along with CB Rashean Mathis returning an interception 61yards for a touchdown. The Colts reclaimed the lead before halftime as RB Joseph Addai got a 3-yard TD run. In the third quarter, Jacksonville regained the lead with RB Maurice Jones-Drew getting a 6-yard TD run. In the fourth quarter, the Jaguars increased their lead with Scobee kicking a 21-yard field goal. Afterwards, Indianapolis responded with Addai's 2-yard TD run. However, the Jaguars got the last laugh as Scobee nailed the game-winning 51-yard field goal. With the loss, the Colts entered their bye week at 1-2.

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