Hoping to rebound from their heartbreaking loss to the Jets, the Broncos remained on home ground for an AFC West rivalry match against the Oakland Raiders. In the first quarter, the Broncos trailed early, as Raiders' quarterback Jason Campbell completed a 43-yard touchdown pass to tight end Zach Miller. The Raiders scored again, after cornerback Chris Johnson returned an interception by quarterback Kyle Orton 30 yards for a touchdown. This was followed by a 4-yard touchdown run by running back Darren McFadden and a 31-yard field goal by placekicker Sebastian Janikowski. Things got much worse for the Broncos in the second quarter, as Campbell threw a 19-yard touchdown pass to McFadden, followed by a McFadden 4-yard touchdown run that gave Oakland a 38-0 lead midway through the second quarter. The Broncos would finally get on the board, with Orton finding running back Knowshon Moreno on a 7-yard touchdown pass, followed in the third quarter by a 27-yard touchdown pass from Orton to Moreno. However, the Raiders struck back, with a 1-yard touchdown run by fullback Marcel Reece, followed by a 57-yard touchdown run by McFadden and a 1-yard touchdown run by running back Michael Bush. Both teams were held scoreless in the fourth quarter. This was the Broncos' worst defeat since a 55-10 loss to the San Francisco 49ers in Super Bowl XXIV. The loss also tied the highest point total that the Broncos have allowed in a single game, since a 59-7 loss to the Kansas City Chiefs in 1963.

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