49ers and Cardinals Clash in Key NFL Matchup on November 16

The San Francisco 49ers will face off against the Arizona Cardinals in Week 11 of the NFL season on November 16, 2025, at State Farm Stadium in Glendale, Arizona. This matchup is particularly significant as both teams vie for playoff positioning, with the 49ers holding a record of 5-5 and the Cardinals standing at 5-4 against the spread.

In their last encounter on September 21, 2025, the 49ers narrowly defeated the Cardinals with a score of 16-15 in Santa Clara, California. This time, the stakes are high as both teams look to capitalize on their remaining games.

Key Player Updates and Injuries

The 49ers are set to welcome back starting quarterback Brock Purdy, who has been sidelined for six games due to a toe injury. Purdy initially injured his toe in the season opener and, despite a brief return in Week 4, re-injured himself. His history against the Cardinals is promising, boasting a passer rating of 120.4 in four previous starts.

On the other side, the Cardinals will be without their top receiver, Marvin Harrison Jr., who underwent surgery for appendicitis earlier this week. This opens the door for third-year wide receiver Michael Wilson, who has accumulated over 500 receiving yards in each of his first two seasons. Wilson will now be the primary target, with 231 receiving yards and one touchdown this season.

In addition to Harrison’s absence, the Cardinals are dealing with several injuries. Quarterback Kyler Murray is set to miss his fifth consecutive game due to a foot injury, remaining on injured reserve for at least two more weeks. Other notable injuries include linebacker Mack Wilson Sr. and wide receiver Zay Jones, who has been placed on IR for the season.

Defensive Matchups and Historical Context

The 49ers have dominated the recent meetings between these teams, winning five of the last seven encounters. However, the Cardinals have a solid home record against San Francisco, boasting a 7-4 mark in their past 11 games at State Farm Stadium.

The 49ers’ defense faces a significant challenge against the Cardinals’ defensive line, which includes veterans Josh Sweat and Calais Campbell. Sweat has recorded eight sacks this season, while Campbell follows closely with five. Their ability to pressure Purdy could be critical, particularly given his injury concerns.

Despite their struggles, the 49ers have shown resilience throughout the season, never losing consecutive games and bouncing back quickly from defeats. Running back Christian McCaffrey continues to impress, becoming the fourth player in NFL history to achieve at least 600 yards rushing and receiving in the first ten games of a season. Conversely, the 49ers have not recorded a run of at least 20 yards this season, marking their longest drought since 1986.

As the 49ers look to improve their performance, they are currently last in the league with just 1.2 sacks per game and have a turnover margin of minus-8, the second worst in the NFL. Meanwhile, the Cardinals rank fourth in forced fumbles and fumble recoveries, showcasing their defensive effectiveness.

With key players returning and others sidelined, this matchup promises to be a thrilling contest as both teams seek to strengthen their playoff aspirations. Fans can expect a strategic battle as the 49ers look to maintain their momentum while the Cardinals aim to capitalize on their home-field advantage.