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With one last chance to get Arizona back in the game, Carson Palmer spotted open tight end Rob Housler near the New Orleans 10-yard line. He threw over Housler's head — right into the hands of rookie safety Kenny Vaccaro.

That fourth-quarter interception capped a difficult day for the Cardinals, who, beyond grabbing a quick 7-0 lead, did little right offensively the rest of the game. As Palmer walked slowly to the sideline, the early advantage had dissolved into a multi-score deficit, and the Cardinals lost 31-7 on Sunday.

Arizona (1-2) moved 80 yards in 11 plays the first time it had the ball, converting two third downs and capping the drive with a 3-yard run by Alfonso Smith. The Cardinals picked up a total of 94 yards and punted seven times on their next seven series, never crossing the Saints 40 until just before Palmer's first of two interceptions.

"We did not play well enough and I did not play well enough to give us a chance to win," Palmer said. "If you didn't convert on third down and you don't move the ball effectively enough on first and second down, and you give that team that many possessions, they are going to score 30-something points."

Arizona held New Orleans (3-0) to minus-6 yards rushing in the first half and still trailed 14-7 at the break. Passing on almost every down, the Saints tried three running plays during the first half, led only 17-7 at the end of the third quarter and still finished with 104 yards rushing as the Cardinals' defense wore down in the fourth quarter.

Palmer went 18 of 35 for 187 yards and was sacked four times. Arizona did not run well, either. Leading rusher Rashard Mendenhall, listed as questionable with a toe injury, gained only 29 yards on nine carries.

"Our defense played great for three quarters and gave us some momentum," Palmer said. "We just didn't give them enough to feed off and give them something to keep fighting for."

The Cardinals came into the game without starting nose tackle Dan Williams, excused because of the death of his father in a car accident as he drove from the family's home in Memphis en route to New Orleans to watch his son play.

Arizona then lost three more defensive starters in the first three quarters. Linebacker Lorenzo Alexander (right foot) and safety Rashad Johnson (finger) left in the first half, with linebacker Sam Acho (sprained left ankle) exiting early in the third quarter.

"We had critical injuries, and some young guys had to chip in and play," said Cardinals coach Bruce Arians, who refused to discuss the severity of the three injuries. "They didn't handle it as well as I hoped they would."

Saints quarterback Drew Brees passed for three touchdowns to go with his 7-yard TD scramble as the Saints improved to 3-0 for the first time since 2009, when they went on to win the Super Bowl.

"Hopefully we can just continue to get a little bit better, and gain confidence and momentum and keep the train rolling," said Brees, who connected twice with tight end Jimmy Graham for scores and once with Robert Meachem. "I'm very happy to be 3-0, 2-0 in the (NFC South) division, 3-0 in the NFC. All those things are significant."

Brees was 29 of 46 for 342 yards. He was intercepted once by New Orleans native and former LSU star Tyrann Mathieu. That play ended a scoring threat, but only delayed the inevitable on a day when Arizona's short-handed defense was little match for the prolific passing attack of the Saints.

Mathieu didn't even seem interested in keeping the football that he caught for his first career interception.

"It's just a regular football," he said. "It doesn't mean anything."

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AP NFL website: www.pro32.ap.org