2025 NFL Picks – Week 11: 49ers at Cardinals

The Matchup. Edge: Cardinals.

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ARIZONA OFFENSE: Poor Jacoby Brissett. He didn’t have a chance. Brissett played much better than Kyler Murray in his first three starts for the Cardinals, but didn’t battle a single defense ranked better than 14th. He took on Seattle’s top-five defense last week and predictably struggled. He was strip-sacked twice in the firt half, setting up two touchdowns for Seattle.

Things will be back to normal for Brissett in this game. That wouldn’t have been the case to start the year, but San Francisco’s defense has been ravaged by injury. Nick Bosa, Fred Warner, and several others have been sidelined for some time. As a result, San Francisco’s defense ranks 28th in the NFL.

The 49ers have no pass rush, so they won’t strip-sack Brissett like the Seahawks. Brissett’s added time in the pocket will make it easy for him to repeatedly connect with Trey McBride and Marvin Harrison Jr. The 49ers are better against the run, but that shouldn’t matter very much because it’s not like the Cardinals rush the ball well anyway.

SAN FRANCISCO OFFENSE: The 49ers have also endured plenty of injuries on this side of the ball. Somehow, Christian McCaffrey has remained unscathed, but San Francisco has been without Brock Purdy and Ricky Pearsall for quite some time.

Jones is another backup quarterback who can’t perform as well versus top defenses. Jones probably wishes he could take on the 49ers defense in real action, especially when it comes to this matchup because the Cardinals are an underrated 12th in defense. They’re better against the run (11th), which will be helpful in containing McCaffrey. The dynamic back was limited to just 52 rushing yards on 17 attempts in the Week 3 matchup.

One area of concern for the Cardinals is their cornerback health. They were down their top two corners against the Seahawks and couldn’t cover Jaxon Smith-Njigba as a result. It remains to be seen if either of the two corners will return to action. If not, Jones will be able to thrive while connecting with Jauan Jennings, who has been hot lately.

RECAP: We’ll have to wait on this one for the injury report. If the Cardinals are able to get at least one of their starting cornerbacks back from injury, Arizona will look like a great play. Backup quarterbacks tend to struggle against quality defenses, so that would apply to Jones in that scenario. We’d also be getting the Cardinals at a ridiculous price of +2.5, or perhaps even +3. I personally made the line Arizona -1.5, yet the current spread is an overreaction to the Cardinals’ blowout loss to the Seahawks, as well as the public’s inaccurate perception of the 49ers.

If, however, the Cardinals will be missing both cornerbacks again, I won’t have much interest in Arizona. I don’t think I’d necessarily back the 49ers, but this would be a non-bet selection on the home underdog.

Check back later, but this might be a two- or three-unit selection on the Cardinals.

THURSDAY THOUGHTS: I don’t know why this line has gone to +3, but I still like Arizona. The Cardinals saw Max Melton return to a limited practice on Wednesday, though Will Johnson was DNP.

SATURDAY NOTES: Brock Purdy and Ricky Pearsall are back for the 49ers. Meanwhile, the Cardinals have injuries all over the place. Marvin Harrison Jr. is out. One of their tackles, Jonah Williams, is out. Top cornerback Will Johnson is out. Starting linebacker Mack Wilson is out. Quality edge rusher Baron Browning is out. Two defensive linemen, including Walter Nolen, are questionable after failing to practice fully all week. I’m going to remove my two units.

SUNDAY MORNING NOTES: The sharps are pounding the 49ers with all of their players back from injury. Also, Arizona has some injury issues.

FINAL THOUGHTS: Again, the sharps are on the 49ers, perhaps because of the severe injury disparity. The best line for Arizona is +3.5 -113 at Bookmaker. You can Bet on WalterFootball’s favorite sportsbook, Bookmaker by clicking the link.

The Motivation. Edge: None.

No edge found.

The Spread. Edge: Cardinals.

WalterFootball.com Calculated Spread: Cardinals -1.5.

Westgate Advance Point Spread: 49ers -1.5.

Computer Model: Cardinals -3.

The Vegas. Edge: Cardinals.

Plenty of money on the 49ers.

Percentage of money on San Francisco: 72% (92,000 bets)

The Trends. Edge: Cardinals.

History: 49ers have won 5 of the last 7 meetings.

Opening Line: 49ers -1.

Opening Total: 48.

Weather: Dome.