Coming off their Sunday night victory over the Broncos, the Seahawks flew to the University of Phoenix Stadium for an NFC West rematch with the Arizona Cardinals. In the first quarter, Seattle trailed early as Cardinals QB Matt Leinart completed a 56-yard TD pass to WR Bryant Johnson, while RB Edgerrin James got a 7-yard TD run.  The Seahawks would respond with QB Matt Hasselbeck completing a 23-yard TD pass to WR D. J. Hackett.  In the second quarter, Arizona increased its lead with kicker Neil Rackers nailing a 32-yard field goal. Seattle would draw closer with Hasselbeck completing a 5-yard TD pass to WR Nate Burleson. In the third quarter, the Seahawks took the lead with Hasselbeck's 2-yard TD pass to WR Darrell Jackson for the only score of the period. However, in the fourth quarter, the Cardinals got the win with Leinart's 5-yard TD pass to WR Larry Fitzgerald and Rackers' 40-yard field goal. With the loss, Seattle fell to 8-5.

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