Coming off their home win over the Panthers, the Titans stayed at home for an AFC South rematch with the Jacksonville Jaguars. In the first quarter, Tennessee trailed early as Jaguars QB Quinn Gray completed a 2-yard TD pass to FB Greg Jones for the only score of the period. In the second quarter, the Titans continued to fall behind as RB Maurice Jones-Drew got an 8-yard TD run. Tennessee would end the half with kicker Rob Bironas getting a 37-yard field goal. In the third quarter, Jacksonville increased its lead with RB Fred Taylor getting a 4-yard TD run. The Titans would manage to get a 49-yard field goal from Bironas. In the fourth quarter, Tennessee drew close with QB Vince Young completing a 20-yard TD pass to WR Justin Gage. Unfortunately, the Jaguars sealed the win with Gray completing a 3-yard TD pass to Jones. Not only was Tennessee's rushing attack held to a season-low 62 yards, but their top-ranked rushing defense allowed its first 100-yard rusher of the year in Maurice Jones-Drew (19 attempts for 101 yards and 1 touchdown). This is largely in part due to DT Albert Haynesworth and DE Travis LaBoy being inactive due to injuries.

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