This Sunday Nov. 16 the San Francisco 49ers (6-4) travel to face the Arizona Cardinals (3-6) at State Farm Stadium in Glendale, Arizona. This NFC West showdown features contrasting trajectories: San Francisco is in the division title race, while Arizona is trending towards the rebuild / evaluation mode.
The 49ers will look to leverage their experience and depth as they aim to solidify their positioning in a crowded West. The Cardinals entering this contest face a steep climb — with key injuries and limited roster stability raising major questions about their competitiveness this week.
Betting markets reflect the tilt: the 49ers are favored (spread around -3) and the total hovers in the high 40s.
Injury & Practice Reports (current as of Nov. 14, 2025)
San Francisco 49ers
Injury report:
RB Christian McCaffrey – Rest (non-injury) – Full practice Thursday.
LT Trent Williams – Rest (non-injury) – Full practice Thursday.
DT Alfred Collins – Hip – Limited participation.
LB Dee Winters – Knee – Limited participation.
WR Ricky Pearsall – Knee – Limited practice.
QB Brock Purdy – Toe (turf-toe variation) – Full participation Thursday, set to start.
QB Mac Jones – Knee – Full practice.
CB Deommodore Lenoir – Calf – Limited practice.
As reported, the 49ers had only four players listed as limited on practice Thursday, and no additional major new injuries.
Arizona Cardinals
Injury report:
WR Marvin Harrison Jr. – Appendicitis (surgery) – DNP.
LB Josh Sweat – Rest / unspecified – DNP.
LB Baron Browning – Concussion – DNP.
CB Will Johnson – Back/Hip – DNP.
T Jonah Williams – Shoulder – DNP.
LB Mack Wilson Sr. – Ribs – DNP.
S Dadrion Taylor-Demerson (Ankle) - DNP
RB Bam Knight (Ankle) - Limited
OL Will Hernandez (Knee) - Limited
OL Kelvin Beachum (NIR-Rest/Groin) - Limited
OL Hayden Conner (Knee) - Limited
LG Evan Brown (Foot) - Limited
DT Walter Nolen III – Knee – Limited.
DL Darius Robinson (Groin) - Limited
LB BJ Ojulari (Knee) - Limited
CB Max Melton – Concussion – Limited.
Arizona’s list is extensive, and multiple starters on defense and offense missed practice Wednesday and Thursday.
Impact of Injuries & Key Storylines
49ers side:
The return of Brock Purdy is the biggest positive for San Francisco. After missing time due to a turf‐toe injury, reports confirm he is ready to resume his starting role.
Ricky Pearsall’s return adds receiving depth and gives the offense another vertical threat. Although he’s back practicing, his knee injury will likely require monitoring.
Defensive depth remains a question - Alfred Collins and Deommodore Lenoir are limited in practice, which could reduce rotation or alignment flexibility for the front seven and secondary.
Overall, the 49ers are trending healthier at an opportune time.
Cardinals side:
Losing Marvin Harrison Jr. to appendicitis surgery is a major blow to Arizona’s offense. His absence removes their top receiving threat and forces the unit to lean on less proven alternatives.
Josh Sweat’s omission from practice is troubling. He leads the pass‐rush and his absence (or limited capacity) could allow the 49ers’ offensive line more time and comfort in protection.
Multiple defensive starters missing or limited (Johnson, Browning, Melton, Nolen) signals that Arizona’s ability to generate pressure and defend the run/pass could be compromised. Depth will be tested.
For Arizona, the timing is brutal: facing a divisional opponent while missing cornerstone pieces on both sides of the ball. The injury wave could accelerate the roster evaluation process and impact competitiveness this week.
Game‐impact implications:
San Francisco’s offense, with Purdy and depth returning, should be able to exploit Arizona’s weakened defense.
Arizona’s offensive limitations — especially without Harrison Jr. — mean fewer explosive threats, putting pressure on the run game and short‐to‐intermediate passing. Against a stout Niners defense, that spells uphill.
The Cardinals’ pass‐rush disruption (absence of Sweat/Browning) gives the 49ers more time to operate, and that can tilt key third-down situations and pocket comfort.
In a matchup between a healthier, playoff‐caliber 49ers squad and a stumbling Cardinals team battling injuries in key spots, the narrative is clear: San Francisco holds the advantage. The return of Brock Purdy and the improved health across the roster give them the tools to assert control. Meanwhile, Arizona’s depleted roster, especially on defense and in the receiving corps, faces an uphill challenge.
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