When the 49ers travel to face in the Cardinals on "Monday Night Football" to close Week 11 of the 2022 NFL season (8:15 p.m. ET, ESPN), they will be going to Mexico City instead of Glendale, Ariz. San Francisco (5-4) will look to take over first place in the NFC West over idle Seattle (6-4), while Arizona (4-6) will try to stay in the NFC wild-card picture.
The 49ers are pretty healthy offensively for the game as their biggest injury issues remain on the defensive front. The Cardinals have two key offensive players, quarterback Kyler Murray (hamstring) and wide receiver DeAndre Hopkins (hamstring), facing game-time decisions. Tight end Zach Ertz (knee) is done for the season and Marquise Brown (ankle) won't yet be activated from injured reserve.
Here's everything to know about betting on 49ers vs. Cardinals in Week 11, including updated odds, trends and our prediction for "Monday Night Football."
49ers vs. Cardinals odds for Sunday Night Football
- Spread: 49ers by 8
- Over/under: 43.5
- Moneyline: 49ers -350, Cardinals +480
The line has held steady by more than a touchdown in the 49ers' favor since early in the week, despite the injury issues piling up for the Cardinals. That's still a pretty hefty number in a neutral site game.
49ers vs. Cardinals all-time series
The 49ers hold a 32-29 edge over their division rivals. The Cardinals narrowed the gap by sweeping the season series in 2021. Surprisingly, they've also taken three of four and 11 of 14.
Three trends to know
—64 percent of spread bettors are thinking the number is too big for the 49ers and are taking the Cardinals to cover
—60 percent of total bettors are going with the over, perhaps tied more to the healthy firepower of the 49ers' offense.
—The 49ers are only 4-5 against the spread this season with only 3 games going over. The Cardinals are 5-5 ATS with also half of their games going over.
Three things to watch
The 49ers' passing offense
The Cardinals will be without top cornerback Byron Murphy Jr. They struggle in coverage vs. the No. 2 wideouts and in the middle. Jimmy Garoppolo should see things open up nicely downfield for Deebo Samuel, Brandon Aiyuk and Jauan Jennings. He can hit for shorter passes that hit after the catch as well as some deep shots.
The Cardinals' rushing offense
They will need to lean more on the run with James Conner given the shaky statuses of Murray and Hopkins with no Brown or Ertz. Their offensive line remains banged up with no left tackle D.J. Humphries. Unfortunately, for them, the 49ers are the No. 2 run defense in the NFL, allowing on average only 82.7 rushing yards per game.
Christian McCaffrey vs. the Cardinals again
The former Panthers feature back gets a second shot vs. Arizona's defense this season. He destroyed the Cards in the passing game with 9 catches on 9 targets for 81 yards and a touchdown. He'll be a tough draw for their linebackers in coverage again.
Stat that matters
8 catches for 78 yards. That's how much on average the Cardinals' defense is giving up in receiving production to the tight end. George Kittle averages 4 catches for 64 yards in this matchup. Kittle can be quiet as a receiver in games when he's dominating as a run blocker, but look for the mighty tight end to become a huge factor in the passing game based on the matchup.
49ers vs. Cardinals prediction
The 49ers have too much offense against a weakened defense. The Cardinals have too little reliable offensive given their injury against a strong overall defense. Nothing has to give south of the border.
49ers 30, Cardinals 17
