San Francisco 49ers vs Arizona Cardinals: Monday Night Football Week 11 preview, picks, top prop bets, more

Nick Bosa 49ers
Nick Bosa (AP Photo/Godofredo A. Vásquez)

The NFL heads to Mexico City for a Monday Night Football showdown between NFC West foes the San Francisco 49ers and the Arizona Cardinals. 

San Francisco 49ers (5-4) at Arizona Cardinals (4-6) 

Game Details:

  • Location: Estadio Azteca in Mexico City, MEX
  • Time: Monday, November 21st at 8:15 p.m. ET
  • Channel: ESPN

Betting Stats:

  • MONEYLINE: SF ML (-365), ARI ML (+285)
  • SPREAD: SF -8
  • OVER/UNDER: 43.5


The Arizona Cardinals are fighting for their playoff lives this weekend as a loss would knock them down to 4-7 and make it a particularly steep climb back to the postseason.

In many ways, this season has been a disaster for Arizona. Their defense, which was top six in the NFL last season, has taken a big step back, and the offense has looked so lost at times that cameras are catching heated sideline exchanges between quarterback Kyler Murray and coach Kliff Kingsbury, as well as between Murray and star wide receiver DeAndre Hopkins. 

The offense certainly won’t be helped by the likely season-ending knee injury to tight end Zach Ertz, and they will also be missing left tackle D.J. Humphries and who has a back injury.

To top it off, Murray is still battling the hamstring injury that kept him out of last week’s game, and while he practiced in a limited capacity this week, it’s not a sure thing that he’ll be under center. His backup, Colt McCoy, returned to full practice Friday after dealing with a knee injury of his own and could be in line to start his second straight game. 

Not an ideal scenario when you’re going up against the 49ers’ number-one-ranked defense. San Francisco is 3rd in the NFL in sacks per pass attempt and 2nd against the run, so their front line, which got back defensive end Jordan Willis last week, is going to put pressure on whoever the Cardinals have under center.

Despite the team’s official Twitter account posted a photo of Hollywood Brown holding a football designed like the Mexican flag with the caption “two days,” the receiver will reportedly not make his return from a foot injury in time to be active on Monday.  

The team desperately needs his deep speed, even though Murray has not taken many chances down the field, even when Brown was active in the early part of the season. On the year, Murray is averaging only four completed air yards per attempt, which is the lowest figure among qualifying NFL quarterbacks. Considering the 49ers are without cornerbacks Jason Verrett and Emmanuel Moseley, who are both out for the season, this might be the week for Arizona to try and take some deep shots. 

When the 49ers have the ball, expect them to keep utilizing their dynamic receiving options and getting them the ball in space. With Christian McCaffrey, Deebo Samuel, and Brandon Aiyuk leading this receiving corps, San Francisco is tops in the NFL with the most average yards after the catch. That’s great news since Arizona’s defense is the worst when it comes to YAC allowed per reception.

Part of that is also that the Cardinals have missed 78 tackles, according to Pro Football Focus, or nearly eight per game. If they do that on Monday, San Francisco is going to make them pay dearly. 

However, while the speedy guys get all the attention, this may finally be the game we see George Kittle get more involved in the offense. The former Pro Bowl tight end has taken a back seat of late, but the Cardinals rank 23rd against the pass and have cracked been beaten all season by tight ends. Over the last two weeks, Noah Fant and Will Dissly combed for 120 yards in Week 9, and Tyler Higbee had 8 catches for 73 yards last week. 

San Francisco now also seems to have a two-headed monster on the ground after Elijah Mitchell returned from injured reserve and gained 89 yards on 18 carries while McCaffrey had just 38 on 14 carries but added another 39 yards through the air. Though Arizona is no slouch against the run, ranking 11th in the NFL in yards allowed per carry and 9th in rushing yards per game. 

With so much up in the air in regard to injuries, it’s unclear how this game will play out. The recent trends seem to point us toward a San Francisco win, but will it be by enough to cover a large spread?


Player Props:

Brandon Aiyuk Over 55.5 receiving yards

We already mentioned how vulnerable Arizona is after the catch and that’s where Aiyuk shines. On top of that, Airyik is averaging 63.0 receiving yards per game, which is already over this prop total. Aiyuk has actually hit this prop in six out of nine games this season and each of his last five. In fact, Aiyuk has over 80 receiving yards in each of his last four, so I like him to hit this on Monday. 

SPORTSBOOK: Bet at DraftKings (-120)


James Conner over 47.5 rushing yards

This may seem like a rough bet considering we talked about how good this 49ers’ defense is against the run, but Conner has been good when he’s been healthy enough to take on a full complement of snaps. He’s hit this total in three of his last four games and missed one by just 2.5 yards. Last week, Conner handled 21 rushes and ran for almost 70 yards and a touchdown. I think he’ll get a similar workload this game, so I like him to go over. 


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Will Colt McCoy start for the Cardinals against the 49ers?
Arizona Cardinals quarterback Colt McCoy throws against the Los Angeles Rams during the first half of an NFL football game Sunday, Nov. 13, 2022, in Inglewood, Calif. (AP Photo/Jae C. Hong)