San Francisco 49ers vs. Arizona Cardinals: Brock Purdy Returns Amid Injuries for Showdown
Sportsgrid Staff
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2025 NFL Week 11 Preview: San Francisco 49ers vs. Arizona Cardinals
The NFC West gives us one of the strangest and most injury-defined matchups of the week: the battered San Francisco 49ers heading to Arizona to face a Cardinals team starting Jacoby Brissett instead of Kyler Murray… and doing so without their top receiver.
The total is 48.5, and that number says everything about how the books view these defenses: vulnerable, inconsistent, and very capable of giving up chunk plays.
Let’s break it down.
San Francisco: Brock Purdy Returns to Stabilize the Chaos
The 49ers have dealt with injuries everywhere—Purdy, Brandon Aiyuk, Ricky Pearsall dings, offensive line shuffling, and secondary issues. But getting Purdy back under center should immediately stabilize the offense.
Why the 49ers Should Move the Ball
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George Kittle is fully involved again
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Ricky Pearsall returning gives them needed explosiveness
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Jauan Jennings continues to be a reliable chain mover
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Kyle Shanahan historically shreds Arizona’s defensive structure
Even with injuries, this offense has too much speed, too much creativity, and too much mismatch potential.
Expect San Francisco to:
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Push tempo
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Attack the seams
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Use layered route concepts to isolate linebackers
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Get Christian McCaffrey 20 touches in space
Arizona’s defense struggles with discipline, and Shanahan is merciless when he finds those weaknesses.
Arizona: Imperfect, Banged Up… But Capable of Scoring
The Cardinals are without:
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Kyler Murray
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Marvin Harrison Jr.
And yet, with Jacoby Brissett, they’re not dead offensively. In fact, they’ve been oddly competent.
Why Arizona Can Score
Brissett brings:
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Stability
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On-time throws
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Smart pre-snap reads
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A willingness to throw inside the numbers
And more importantly:
This 49ers defense is not the 49ers defense of the past three years.
They’re beat up:
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No consistent pass rush outside Bosa
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Secondary miscommunications
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Linebackers being asked to cover too much ground
Arizona has enough:
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Trey McBride
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Greg Dortch
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Bam Knight / Emari Demercado types
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Gadget packages
…to string together drives.
It’s not fireworks—but it’s points.
Expect Offense on Both Sides
Between:
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Defensive injuries
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Defensive regression
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Multiple offensive mismatches
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Tempo potential
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Shanahan’s creativity
…this is quietly a game with shootout potential.
Arizona’s defense is bottom-tier by EPA and explosive plays allowed. San Francisco’s defense is middle-of-the-pack and trending downward with injuries.
This is why:
48.5 feels low.
This game profiles more like:
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27–24
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30–23
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31–27
…than the grind-it-out divisional slugfests of past years.
Betting Angle
This matchup is filled with actionable angles.
Side
Lean: 49ers – the points
Even injured, San Francisco has the better QB, better scheme, better weapons, and a coaching advantage that typically shows up against division rivals.
Shanahan vs. Arizona has been one-sided for years.
Total (48.5)
Strong Lean: Over
This might be the best total on the entire Week 11 board.
Reasons:
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Both defenses are compromised
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Both offenses have matchup advantages
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Arizona plays faster at home
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Purdy’s return elevates San Francisco’s efficiency
Books posted a mid-range number because of injuries. But the injuries actually help the Over, not the Under.
Prop Angles
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Brock Purdy Over Passing Yards → Arizona can’t generate pressure consistently
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Christian McCaffrey Anytime TD → Always live, especially vs. Arizona
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George Kittle Longest Reception Over → Exploit the middle of the field
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Jacoby Brissett Over Completions → Volume-driven, playing from behind
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Trey McBride Receptions Over → Arizona’s offensive focal point
This is a great spot for player props across the board.
Final Thoughts
This matchup looks messy on paper because of the injuries, but it’s actually one of the most fantasy-friendly and betting-friendly games of the week. Shanahan has the advantage, Purdy’s return boosts the Niners’ rhythm, and Arizona is capable enough to keep pace.
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