San Francisco 49ers vs. Arizona Cardinals: Major Injuries, Key Absences, Odds, and Full Game Breakdown

The highly anticipated NFC West clash between the San Francisco 49ers vs. Arizona Cardinals has taken a dramatic turn before kickoff, with both teams facing major injury concerns. With playoff implications already on the line early in the season, fans are bracing for a showdown that could reshape the division standings.

49ers Hit Hard by Key Injuries

The 49ers have been hit by a series of injuries that significantly impact their game plan. Quarterback Brock Purdy (toe and shoulder) and wide receiver Jauan Jennings (ankle and shoulder) have been ruled out, forcing San Francisco to rely on backup Mac Jones under center. Tight end George Kittle also remains unavailable, leaving the passing game thin on proven targets.

On the offensive line, the loss of Spencer Burford to injured reserve with a knee injury adds further strain. Ben Bartch’s absence compounds the issue, meaning the 49ers will be reshuffling protection schemes against Arizona’s defense.

Defensively, star edge rusher Nick Bosa was sidelined with a knee injury in the first quarter and will not return. Rookie lineman Mykel Williams briefly exited with a wrist issue but managed to come back later in the game.

49ers Notable Injuries

Cardinals Face Their Own Setbacks

The Arizona Cardinals are also dealing with critical absences. Left tackle Paris Johnson Jr. was ruled inactive, removing a key piece of protection for quarterback Kyler Murray. Running back James Conner left the game with an ankle injury and was later ruled out, leaving Arizona to lean on Emari Demercado and rookie Trey Benson in the backfield.

Cardinals Notable Injuries

• Paris Johnson Jr. – Left Tackle (inactive)

• James Conner – Running Back (ankle, ruled out)

These setbacks place additional pressure on Arizona’s offensive line and rushing attack, forcing them to adapt against a 49ers defense missing its own stars.

Offensive Adjustments and Player Roles

With Purdy sidelined, Mac Jones has taken over as quarterback for the 49ers. He will be tasked with managing the offense under difficult circumstances, relying heavily on Christian McCaffrey, who is expected to play a dual role as both a runner and receiver.

San Francisco’s receiving unit is now headlined by Ricky Pearsall, Kendrick Bourne, Marquez Valdes-Scantling, Skyy Moore, and Malik Turner, who was elevated from the practice squad. Their ability to step up will define whether the 49ers offense can maintain efficiency.

Meanwhile, Arizona will test its depth in the run game. Without Conner, Demercado and Benson are projected to share carries, which could alter the Cardinals’ offensive rhythm.

Game Time, Broadcast, and Odds

The San Francisco 49ers vs. Arizona Cardinals game is set at Levi’s Stadium, with kickoff scheduled for 1:25 p.m. PT. Fans can catch the action on FOX or tune in via the 49ers Radio Network.

Game Details

Matchup Implications in the NFC West

This contest carries weight beyond the box score. Both teams entered the week undefeated at 2–0, and the winner will gain early momentum in the NFC West race.

Key factors that could decide the outcome include:

• Whether Mac Jones can command the 49ers offense effectively.

• Christian McCaffrey’s ability to carry a heavier offensive workload.

• The impact of Nick Bosa’s absence on San Francisco’s pass rush.

• How Arizona’s backup running backs perform against a still-tough 49ers defensive front.

• Kyler Murray’s playmaking ability under increased pressure without key blockers.

The stage is set for a gritty divisional battle where depth, resilience, and playmaking will decide which side emerges with the upper hand.