Hoping to rebound from their blowout loss at Green Bay, the Broncos returned home for an AFC West duel with the San Diego Chargers. The Chargers took the early lead in the first quarter, with a 24-yard field goal by placekicker Nick Novak. The Broncos grabbed the lead, when cornerback Cassius Vaughn returned an interception off Chargers' quarterback Philip Rivers 55 yards for a touchdown. The Chargers responded, with a 32-yard field goal by Novak. The Broncos extended their lead in the second quarter, with a 32-yard field goal by placekicker Matt Prater. However, the Chargers would re-claim the lead, with a 2-yard touchdown run by Rivers, a 28-yard field goal by Novak, followed by a 42-yard touchdown pass from Rivers to wide receiver Malcom Floyd, giving San Diego a 23-10 halftime lead. The Broncos benched quarterback Kyle Orton in favor of Tim Tebow. After a scoreless third quarter, the Chargers added to their lead, with a 51-yard field goal by Novak. The Broncos responded, when Tebow scrambled for a 12-yard touchdown (with a two-point conversion run by running back Willis McGahee), then threw a 28-yard touchdown pass to running back Knowshon Moreno (with a failed two-point conversion attempt), to pull the Broncos to within 26-24 with just over three minutes left in the game. The Chargers responded, with a 35-yard field goal by Novak. The Broncos tried to rally with 24 seconds remaining in regulation, but Tebow's last-second desperation pass into the end zone was unsuccessful, sealing the win for San Diego. Defensive tackle Kevin Vickerson suffering an ankle injury early in the game. Though he later returned, he was placed on injured reserve one day later (October 10).

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