Venue & Logistics
Venue: Levi’s Stadium, Santa Clara, California
Kickoff Time: 4:25 PM ET / 1:25 PM PT
Broadcast: FOX: Adam Amin, Mark Sanchez, Kristina Pink (field reporter)
Weather Forecast (Santa Clara, CA)
Conditions: Sunny, warm
Temperature: ~81°F (27°C) at kickoff, cooling to 75°F (24°C) by the fourth quarter
Winds: 6–9 mph from the northwest
Precipitation:
Impact: Minimal; excellent football weather
Injury Report
Arizona Cardinals:
LB Cody Simon – Questionable
TE Tip Reiman – Questionable
G Will Hernandez – Questionable
CB Will Johnson – Questionable
CB Garrett Williams – Questionable
San Francisco 49ers:
QB Brock Purdy – Out (shoulder, expected return Week 4)
QB Mac Jones – Starting
CB Siran Neal – Questionable
G Ben Bartch – Out
OT Spencer Burford – Questionable
WR Jauan Jennings – Questionable
Key Player Matchups
Kyler Murray (ARI) vs. 49ers’ Pass Rush – Murray has 383 yards, 3 TDs, 1 INT through two games; San Francisco’s front will look to contain his mobility.
Mac Jones (SF) vs. Cardinals’ Secondary – Jones threw for 279 yards and 3 TDs in Week 2; Arizona’s secondary is banged up.
Trey Benson (ARI) vs. 49ers’ Run Defense – Benson leads Arizona with 83 rushing yards; San Francisco has allowed just 3.8 YPC.
Christian McCaffrey (SF) vs. Cardinals’ Front Seven – McCaffrey has 124 rushing yards through two games; Arizona’s defense has been stout against the run.
Trey McBride (ARI) vs. 49ers’ Linebackers – McBride leads Arizona with 139 receiving yards; Fred Warner and Dre Greenlaw will be tested in coverage.
Recent Team Form
Arizona Cardinals (2-0):
W vs. Carolina Panthers 27-22 (Week 2)
W @ New Orleans Saints 20-13 (Week 1)
Offense averaging 23.5 PPG; defense allowing 17.5 PPG.
San Francisco 49ers (2-0):
W vs. New Orleans Saints 26-21 (Week 2)
W @ Seattle Seahawks 17-13 (Week 1)
Offense averaging 21.5 PPG; defense allowing 17.0 PPG.
Series History
All-Time Meetings: 49ers lead 36–31
Most Recent: 49ers swept Cardinals in 2024
Trend: San Francisco has won 5 of the last 6
Betting Trends
Cardinals are 2-0 ATS in 2025
49ers are 1-1 ATS in 2025
The Under has hit in 3 of the last 4 meetings
Cardinals are 4-1 ATS in last 5 road games
49ers are 6-2 SU in last 8 home games
Historical Betting Results
2024 (Week 15): 49ers -7.5, won 27-14 → Cover, Under
2024 (Week 4): 49ers -14, won 35-16 → Cover, Over
2023 (Week 15): 49ers -12.5, won 45-29 → Cover, Over
2023 (Week 4): 49ers -14, won 35-16 → Cover, Over
CARDINALS NOTES:
• QB KYLER MURRAY totaled 252 yrads (220 pass, 32 rush) & had TD pass last week. Aims for his 4th in row with 90+ rating & 6th in row with TD pass. Passed for 4 TDs vs. 0 INTs for 128.5 rating in last meeting. Aims for his 4th in row at SF with rush TD. • RB JAMES CONNER had 60th-career rush TD last week. Aims for his 3rd in row with TD. Had 100 scrimmage yards (86 rush, 14 rec.) in last meeting & has 50+ scrimmage yards in 6 of his 7 career games vs. SF. • TE TREY MCBRIDE had 6 catches for 78 yards last week. Has 6+ catches in 8 of his past 9 & aims for his 5th in row with 6+ receptions. Had rec. TD in last meeting. Aims for his 4th in row vs. SF with 6+ catches & 50+ rec. yards. Since 2023, has 22 games with 5+ receptions, most among NFL TEs. • WR MARVIN HARRISON JR. aims for his 3rd in row on road with 5+ catches & 70+ rec. yards. Had 5 catches for 63 yards & rec. TD in last meeting. • WR MICHAEL WILSON had 1st rec. TD of season in Week 2. Had 5 catches for 78 yards in last road meeting (10/6/24). • DL CALAIS CAMPBELL became 4th player since 1982 with 2+ sacks in game at age 39-or-older in Week 2, joining James Harrison, Clay Matthews & HOFer Bruce Smith (3x). Has 15 TFL in 19 career games vs. SF. • LB JOSH SWEAT had 1st sack of season & 8th-career FF last week. • LB BARON BROWNING had 2nd-career INT last week. Aims for his 3rd in row with TFL. • LB MACK WILSON aims for his 3rd in row with 8+ tackles & PD. Had INT in last road meeting & aims for his 3rd in row vs. SF with PD. • LB ZAVEN COLLINS had 1st-career FR-TD in Week 2. Had sack & FF in last meeting. • CB DENZEL BURKE (rookie) set career high with 3 PD in Week 2. • CB WILL JOHNSON (rookie) aims for his 3rd in row with PD. • S BUDDA BAKER aims for his 13th in row vs. SF with 5+ tackles. • S JALEN THOMPSON led team with 10 tackles in Week 2.
49ERS NOTES:
• QB MAC JONES passed for 279 yards & 3 TDs vs. 0 INTs for 113.1 rating in SF debut last week, his 2nd-career game with 275+ pass yards & 3+ TD passes. Has 20+ completions & 30+ pass atts. in 6 of his past 7 starts overall. • RB CHRISTIAN MCCAFFREY had 6 catches, 107 scrimmage yards (55 rush, 52 rec.) & 30th-career TD catch in Week 2 & became 3rd player ever with 50+ career rush TDs (52) & 30+ career rec. TDs. Is 1 of 3 (James Cook & Bijan Robinson) with 100+ scrimmage yards in each of 1st 2 weeks. Can become 1st player since HOFer Marshall Faulk (2000) with 50+ rush yards & 50+ rec. yards in each of 1st 3 weeks of season. Has 1,609 scrimmage yards (107.3 per game) & 16 TDs (10 rush, 6 rec.) in 15 home games with SF since 2022. Aims for his 6th in row at home with 100+ scrimmage yards. Aims for his 3rd in row vs. Ari. with 175+ scrimmage yards & 3+ TDs & has 100+ scrimmage yards in 6 of his 7 career games vs. Ari. • RB BRIAN ROBINSON aims for his 3rd in row vs. Ari. with TD. • WR JAUAN JENNINGS had 5 catches for team-high 89 yards & 1st rec. TD of season in Week 2. Had 7 catches for 52 yards in last meeting. • WR RICKY PEARSALL aims for his 5th in row with 50+ rec. yards. Had TD catch in last meeting. • LB FRED WARNER led team with 11 tackles & had TFL, PD, FF & FR last week. Aims for his 3rd in row vs. Ari. & 5th in row overall with TFL. • DL NICK BOSA aims for his 3rd in row with sack. Has 35 sacks & 46 TFL in 42 career home games. Had 2 TFL & INT in last home meeting. • DL BRYCE HUFF had 1st sack of season & 3rd-career FF last week. • DL MYKEL WILLIAMS (rookie) had 1st 2 career TFL in Week 2. • CB UPTON STOUT (rookie) had 1st career sack last week. • CB RENARDO GREEN has PD in 10 of his past 11 & aims for his 6th in row with PD. Had career-high 3 PD in last meeting.
Game Odds
Arizona Cardinals 45.5
San Francisco 49ers – 3
Odds Courtesy of Sports Odd Direct as of Saturday, September 20, 2025
