by Rod Pearson
Friday, Nov 14, 2025
Game Time: 4:05 pm ET, Sunday, November 16, 2025
Venue: State Farm Stadium, Glendale, AZ
Where to Watch: FOX
Opening Odds at USA Sportsbooks
DraftKings: Point Spread: 49ers -3, Cardinals +3; Over/Under: 48.5 points
Bet365: Point Spread: 49ers -3, Cardinals +3; Over/Under: 48.5 points
BetMGM: Point Spread: 49ers -3, Cardinals +3; Over/Under: 48.5 points
Season Record
San Francisco 49ers: 6-4 (3rd place, NFC West)
Arizona Cardinals: 3-6 (4th place, NFC West)
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San Francisco 49ers: lost their last game at home against the Los Angeles Rams 42-26.
Arizona Cardinals: lost their last game on the road against the Seattle Seahawks 44-22.
San Francisco 49ers vs Arizona Cardinals Preview and Analysis
The 49ers are entering this game with a 6-4 record overall and they have a 3-1 record in their divisional games too. They are 2-2 in their home games, 4-2 in their road games, and they are also 0-0 in their neutral site games this season, but they will be on the road for this game. They lost their last game against the Los Angeles Rams 42-26. Mac Jones was the starting QB and he completed 33/39 passes for 319 passing yards, 3 touchdowns, and 1 interception. Brian Robinson Jr. led the team in rushing yards with 41 and 1 TD. George Kittle led the receivers with 84 receiving yards on 9 receptions and 1 TD. Dee Winters led the defense in that game with 5 solo tackles and 3 assisted tackles while Kalia Davis and Keion White each led the defense in sacks with 0.5. No one on the defense came away with an interception for them in that one.
The Cardinals are entering this game with a 3-6 record overall and they have a 0-3 record in their divisional games too. They are 1-3 in their home games, 2-3 in their road games, and they are also 0-0 in their neutral site games this season, but they will be at home for this game. They lost their last game against the Seattle Seahawks 44-22. Jacoby Brissett was the starting QB and he completed 22/44 passes for 258 passing yards, 2 touchdowns, and 0 interceptions. Emari Demercado led the team in rushing yards with 64. Trey McBride led the receivers with 127 receiving yards on 9 receptions and 1 TD. Jalen Thompson led the defense in that game with 5 solo tackles and 0 assisted tackles while Josh Sweat led the defense in sacks with 1. Denzel Burke came away with the only interception for them in that one.
49ers vs Cardinals Prediction
The current betting odds have the 49ers listed as a 3 point favorite in this game according to Draftkings Sportsbook. The 49ers have looked good in their games this season with their 6-4 record overall, but that record has them near the bottom of the NFC West in a really competitive division. They have been finding ways to win games even though they have been dealing with a lot of injuries, but they are starting to get healthier now. Meanwhile, the Cardinals have looked terrible in their games this season with their 3-6 record overall which has them right at the bottom of the NFC West. They are off a 44-22 loss to the Seahawks in their last one and they were out of that game by the end of the 1st quarter. They have been struggling all season, but they have also been missing their starting QB over the last few weeks. The team has looked better at times without Kyler Murray, but now they have a lot of other injuries starting to pile up too. Brissett hasn't looked terrible in his starts, but he looked bad last week and now with all of the injuries, he doesn't have a lot of talent left on the offense to throw to. The 49ers are still the much better team on both sides of the ball, starting to get healthier now too, and this is a must win divisional game for them with the state of the division. The best way to place a bet here is on the 49ers to cover the spread in this game.
49ers Cardinals Prediction: Our NFL Pick for Sunday, November 16, 2025 (4:05 pm ET start time) is 49ers 24 Cardinals 10.
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NFL Betting Trends
San Francisco 49ers: 19-27 ATS in all games. 13-23 ATS in games played on a grass field. 1-3 ATS off a home loss against a division rival. 27-18 OVER in all games. 12-6 OVER in a road game where the total is between 42.5 and 49 points. 11-3 OVER after playing a division game.
Arizona Cardinals: 21-12 ATS as an underdog. 9-4 ATS after allowing 30 points or more last game. 4-1 ATS after a 2 game road trip. 14-6 OVER in home games. 12-5 OVER in a home game where the total is between 42.5 and 49 points. 13-6 OVER after playing their last game on the road.
Key Injuries
San Francisco 49ers: D. Lenoir (CB) Injured - Calf. T. Williams (OT) Injured - Rest. C. McCaffrey (RB) Injured - Rest. M. Jones (QB) Injured - Knee. B. Purdy (QB) Injured - Toe. D. Winters (LB) Injured - Knee. R. Pearsall (WR) Injured - Knee. A. Collins (DL) Injured - Hip.
Arizona Cardinals: J. Sweat (LB) Injured - Rest. H. Conner (OG) Injured - Knee. K. Beachum (OG) Injured - Groin. J. Williams (OG) Injured - Shoulder. M. Wilson Sr. (LB) Injured - Ribs. B. Nichols (DL) Injured - Personal. E. Brown (OG) Injured - Foot. W. Hernandez (OG) Injured - Knee. B. Browning (LB) Injured - Concussion. B. Knight (RB) Injured - Ankle. B. Ojulari (LB) Injured - Knee. M. Melton (CB) Injured - Concussion. X. Weaver (WR) Injured - Ankle. M. Harrison Jr. (WR) Injured - Illness. D. Robinson (DL) Injured - Groin. D. Taylor-Demerson (S) Injured - Ankle. W. Nolen III (DL) Injured - Knee. W. Johnson (CB) Injured - Back.
Notable Quotes
“We knew it would be a big challenge going in. We know how good they are. We thought we could slow them down and find a way to get them off on third down. We obviously didn’t do that very well.” - Kyle Shanahan after his team’s loss against the LA Rams in their last game.
“Just got behind early versus a good team. It’s tough to dig yourself out, so not a lot of good from out of that game.” - Jonathan Gannon after his team’s loss against the Seahawks in their last game.
Starting Lineups
San Francisco 49ers
WR Bourne, Kendrick
WR Robinson, Demarcus
WR Jennings, Jauan
TE Kittle, George
QB Jones, Mac
RB McCaffrey, Christian
FB Juszczyk, Kyle
Arizona Cardinals
WR Harrison Jr., Marvin
WR Wilson, Michael
WR Dortch, Greg
TE McBride, Trey
QB Brissett, Jacoby
RB Demercado, Emari
Statistical Leaders
San Francisco 49ers
Passing: Mac Jones (2,151)
Rushing: Christian McCaffrey (626)
Receiving: Christian McCaffrey (692)
Touchdowns: Christian McCaffrey (8)
Arizona Cardinals
Passing: Jacoby Brissett (1,118)
Rushing: Emari Demercado (233)
Receiving: Trey McBride (603)
Touchdowns: Trey McBride (6)
Coaches:
San Francisco 49ers: Kyle Shanahan (9th season)
Arizona Cardinals: Jonathan Gannon (3rd season)
Rod Pearson
About the Author:
Rod Pearson has been a rabid sports fan his entire life. He grew up in Ontario, and was skilled in both hockey and baseball, and pitched in an elite baseball league for many years. In 2022, Rod decided to hang up his glove, so that he could write about the sports he loves -- but from a gambling perspective. Join Rod every day as he breaks down the games to find the best betting value.
