Cardinals vs. 49ers Odds & Betting Predictions - September 21, 2025

Cardinals at 49ers

8:25 pm • FOX

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Arizona Cardinals

@

San Francisco 49ers

MatchupOpenSpreadTotalMoneyline
Cardinals 1-0	+3.5	+1.5-115	o42.5-110	-110
49ers 1-0	u47.5	-1.5-105	u42.5-110	-120

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Sunday 8:25 p.m.

September 21, 2025

Levi's StadiumSanta Clara

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72°Fahrenheit

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0%Rain

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4Wind

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NFL Public Betting

49ers are 1-0 in their last 5 games.
49ers are 1-0 in their last 5 games against the spread
49ers are 1-0 in their road games against the spread
The totals have gone OVER in 0 of 49ers' last 1 games

Against the Spread (ATS) History

	overall	home	away	favorite	underdog
49ers	1-0	N/A	1-0	1-0	N/A
Cardinals	1-0	N/A	1-0	1-0	N/A

Over/Under History

	overall	home o/u	away o/u	favorite o/u	underdog o/u
49ers	0-1	N/A	0-1	0-1	N/A
Cardinals	0-1	N/A	0-1	0-1	N/A

Straight-Up (ML) History

	overall	home	away	favorite	underdog
49ers	1-0	N/A	N/A	1-0	N/A
Cardinals	1-0	N/A	N/A	1-0	N/A

date	opponent	score	spread	over/under	moneyline
Sep 7th	@SEA	W 17-13	-2.5 W	U 43.5	SF -132
Aug 24th	LAC	W 30-23	+2.5 W	O 35.5	SF +125
Aug 16th	@LV	W 22-19	+4.5 W	O 40.5	SF +180
Aug 10th	DEN	L 9-30	+6.5 L	O 38.5	DEN +240
Jan 5th	@ARI	L 24-47	+5.5 L	O 43.5	ARI +195

Demarcus Robinson
WR
Robinson is out with suspension
Out
George Kittle
TE
Kittle is out with hamstring
Out

Eddy Pineiro
K
Pineiro is questionable with knee
Questionable
Brandon Aiyuk
WR
Aiyuk is out with knee
Out
Jauan Jennings
WR
Jennings is questionable with shoulder
Questionable
Brock Purdy
QB
Purdy is out with toe
Out
Jacob Cowing
WR
Cowing is out with hamstring
Out
Jordan Watkins
WR
Watkins is doubtful with ankle
Doubtful
Jordan James
RB
James is doubtful with finger
Doubtful

Will Hernandez
OL
Hernandez is out with knee
Out
Owen Pappoe
LB
Pappoe is questionable with quad
Questionable
Dante Stills
DE
Stills is questionable with heel
Questionable

See more NFL Injuries

passing yards
Brock Purdy
277
pyds
passing touchdowns
Brock Purdy
2
ptd
rushing yards
Christian McCaffrey
69
ryds
rushing touchdowns
-
-
rtd

	Starter	2ND	3RD	4TH
QB	Brock Purdy	Mac Jones	Kurtis Rourke
RB	Christian McCaffrey	Isaac Guerendo	Jordan James
WR	Jauan Jennings	Jacob Cowing	Skyy Moore	Junior Bergen
TE	George Kittle	Luke Farrell	Jake Tonges	Brayden Willis
LT	Trent Williams	Spencer Burford
LG	Ben Bartch	Nick Zakelj
C	Jake Brendel	Matt Hennessy	Drake Nugent
RG	Dominick Puni	Connor Colby	Drew Moss
RT	Colton McKivitz	Austen Pleasants
LDE	Nick Bosa	Yetur Gross-Matos	Robert Beal
RDE	Mykel Williams	Bryce Huff	Sam Okuayinonu	Trevis Gipson
WLB	Dee Winters	Nick Martin	Jalen Graham
MLB	Fred Warner	Luke Gifford	Tatum Bethune	Curtis Robinson
LCB	Renardo Green	Jakob Robinson
SS	Ji'Ayir Brown	Malik Mustapha	Derrick Canteen
FS	Jason Pinnock	Marques Sigle	Siran Neal
RCB	Deommodore Lenoir	Darrell Luter
P	Thomas Morstead
PR	Jacob Cowing	Junior Bergen	Jordan Watkins	Ricky Pearsall
KR	Isaac Guerendo	Junior Bergen
LS	Jon Weeks
FB	Kyle Juszczyk
DT	Kevin Givens	Alfred Collins	Sebastian Valdez	Evan Anderson
RWR	Ricky Pearsall	Jordan Watkins	Malik Turner
NT	Jordan Elliott	C.J. West	Kalia Davis
LWR	Brandon Aiyuk	Russell Gage	Malik Turner
NB	Upton Stout	Chase Lucas

Total

Passing

130

YDS

265

21/29

Comps/Atts

26/35

5.621

YPA

7.914

2/0

TDs/INTs

2/2

5/33

Sacks/Yards

1/12

Rushing

146

Rush Yards

119

27

Attempts

36

5.407

YPC

3.306

0

TDs

0

Turnovers

Fumbles Lost

0

Interceptions

2

Efficiency

2/3 66.67%

Redzone

2/5 40%

6/13 0%

3rd Down

7/14 0%

0/0 0%

4th Down

2/2 0%

First Downs

19

Total

24

11

Pass

15

5

Rush

7

3

Penalty

2

Misc

/

Penalties/Yards

/

Possession

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MatchupOverUnder
Cardinals 1-0	N/A	N/A
49ers 1-0	N/A	N/A