The Rams' sixth game was an Interconference duel against the San Diego Chargers inside their dome. In the first quarter the Rams took the early lead as kicker Josh Brown made a 39-yard field goal, followed by QB Sam Bradford completing a 38-yard TD pass to WR Danario Alexander. The Rams increased their lead in the 2nd quarter when RB Steven Jackson got a 7-yard TD run. The Chargers replied with kicker Nate Kaeding nailing a 41-yard field goal, followed in the third quarter by FB Mike Tolbert getting a 1-yard TD run. In the 4th quarter the Rams' lead increased again when Josh Brown hit a 48-yard field goal, but was cut when QB Philip Rivers made a 5-yard TD pass to WR Buster Davis. With the win, the Rams improved to 3-3 snapping their 13-game losing streak against AFC Opponents.

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