Coming off a season-sweep over the Raiders, the Chargers flew to Ralph Wilson Stadium for a cold Week 13 fight against the throwback-clad Buffalo Bills. This game would also mark the return of San Diego's star linebacker Shawne Merriman after his four-game suspension for failing a test for performance-enhancing drugs. In the first quarter, the Chargers drew first blood with kicker Nate Kaeding's 42-yard field goal and RB LaDainian Tomlinson's 51-yard TD run. In the second quarter, San Diego got the only score of the period with QB Philip Rivers completing an 11-yard TD pass to TE Antonio Gates. In the third quarter, the Bills started to come back with QB J. P. Losman completing a 5-yard TD pass to TE Robert Royal, while RB Willis McGahee got a 2-yard TD run. In the fourth quarter, the Chargers distanced themselves from Buffalo with Tomlinson's 2-yard TD run. The Bills would get another touchdown, with Losman completing a 6-yard pass to WR Peerless Price. San Diego would emerge as the victor. With their sixth-straight win, the Chargers improved to 10-2.

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