The San Francisco 49ers are optimistic about the return of quarterback Brock Purdy, who is set to play against the Arizona Cardinals on Sunday at 4:05 p.m. EDT. Purdy has been sidelined for six games due to a toe injury sustained in the season opener.
The 49ers, currently holding a 6-4 record, will face the struggling Cardinals, who sit at 3-6. The odds from BetMGM list the 49ers as favorites by 2.5 points. In their last meeting, the 49ers narrowly defeated the Cardinals 16-15 on September 21, 2025.
Purdy initially injured his toe in the season opener, missing two subsequent games. He returned in Week 4 but re-aggravated the injury, resulting in his extended absence. Notably, he possesses the highest passer rating of any player with at least three starts against the Cardinals, boasting a rating of 120.4.
For the Cardinals, the absence of their top receiver, Marvin Harrison Jr., due to appendicitis surgery significantly impacts their offensive strategy. In his place, third-year receiver Michael Wilson will step up as the primary target. Wilson has shown promise with over 500 receiving yards during his first two seasons and has accumulated 231 yards and one touchdown this year.
The Cardinals” defensive line, featuring veterans Josh Sweat and Calais Campbell, has demonstrated the ability to pressure quarterbacks effectively. Sweat has recorded eight sacks, while Campbell has five. They will aim to test Purdy”s mobility early in the game to see how he handles his injured toe.
In addition to Purdy”s anticipated return, the 49ers expect Ricky Pearsall to return after a six-game absence due to a knee injury. Defensive tackle Alfred Collins may also rejoin the lineup after missing last week”s game due to a hip injury.
On the injury front for the Cardinals, quarterback Kyler Murray will miss his fifth consecutive game due to a foot injury and remains on injured reserve for at least two more games. Other notable absences include receiver Zay Jones, placed on IR due to an Achilles tendon injury, and starting linebacker Mack Wilson because of rib issues. Several other players, including linebacker Baron Browning and safety Dadrion Taylor-Demerson, are also dealing with injuries.
Historically, the 49ers have won five of the last seven matchups against the Cardinals, although Arizona holds a 7-4 record against San Francisco in their previous eleven games at State Farm Stadium. The 49ers have not lost consecutive games all season and have shown resilience, winning every game following a loss so far.
Running back Christian McCaffrey has also made headlines, becoming the fourth player in NFL history to achieve at least 600 rushing yards and 600 receiving yards within the first ten games of a season. However, the 49ers have struggled with their rushing game, averaging 94.8 yards per game, the lowest since 2007.
As the game approaches, all eyes will be on Purdy”s performance and how the 49ers adapt their strategy with key players returning to the field.
