The 49ers began their season at Qwest Field for an NFC West match against the Seattle Seahawks.  In the first quarter, the Niners had the early lead when kicker Joe Nedney made a 23-yard field goal, which was extended in the second quarter when Nedney made another 23-yard field goal. Then, San Francisco failed to maintain it and then fell behind when Seahawks quarterback Matt Hasselbeck got a 1-yard touchdown run, followed by him making a 13-yard touchdown pass to wide receiver Deon Butler. In the third quarter, the 49ers struggled further when quarterback Alex Smith threw an interception to cornerback Marcus Trufant, which was returned 32 yards for a touchdown. This was followed by Hasselbeck's 3-yard touchdown pass to wide receiver Deion Branch. In the fourth quarter, the Niners continued to struggle when kicker Olindo Mare made a 35-yard field goal.

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