The Arizona Cardinals are coming off their first loss of the season last Thursday and head into Sunday’s game versus the San Francisco 49ers with a ton of injuries to key offensive players including quarterback Kyler Murray, who is questionable.
The 49ers are coming off a 33-22 win at Chicago last week but are still just 1-4 SU in their last five and lost 17-10 as six-point road dogs versus the Cardinals in Week 5. Arizona comes into this NFC battle tied for the best record in the division and a slight 1-point favorite, with the total sitting at 46.
If you’re betting this game on Sunday, November 7, then make sure you read our free NFL betting picks and predictions for the Cardinals vs. 49ers first.
Cardinals vs 49ers odds
Odds via the Covers Line, an average comprised of odds from multiple sportsbooks.
This game was as high as ARI -3.5 on the look-ahead, opened at -2.5 and bounced around from a pick ‘em to ARI -1. The total has fallen through the key number of 47 and sits at 46. Use the live odds widget above to track any future line movements right up until kickoff and be sure to check out the full NFL odds before placing your bets.
Cardinals vs 49ers picks
Picks made on 11/04/2021 at 1:10 p.m. ET.
Click on each pick to jump to the full analysis.
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Cardinals vs 49ers game info
• Location: Levi's Stadium, Santa Clara, CA
• Date: Sunday, November 7, 2021
• Time: 4:28 p.m. ET
• TV: FOX
Cardinals at 49ers betting preview
Cardinals: DeAndre Hopkins WR (Out), Kyler Murray QB (Out), Rashard Lawrence DT (Out), Jonathan Ward RB (Out), JJ Watt DE (Out), Kevin Peterson CB (Out), James Wiggins S (Out).
49ers: Aaron Banks OL (Out), Trey Semon RB (Out), Anthony Zettel DT (Out), Maurice Hurst DT (Out), Jaquiski Tartt S (Out), Tarvarius Moore S (Out), Charles Omenihu DL (Out).
Find our latest NFL injury reports.
Betting trend to know
The Under is 7-0 in the Cardinals' last seven games as a road favorite. Find more NFL betting trends for Cardinals vs. 49ers.
Cardinals vs 49ers predictions
Cardinals -1 (-110)
The main story in Sunday’s NFC West battle is the health of Arizona quarterback Kyler Murray, who injured his ankle last Thursday and is listed as questionable after remaining sidelined for Thursday’s practice. Coach Kliff Kingsbury is optimistic that Murray can make the start even if he doesn’t practice this week. Arizona were six-point favorites at home versus the 49ers in Week 5, so this ARI -1.5 is already reflecting the health concerns of the Arizona QB.
If Murray does get the call, and not veteran back-up Colt McCoy, Murray will likely have to find some success in the pocket as the 49ers have a Top-10 success rate against the run but struggle more in the passing game and have some injuries at the safety position. Even with the injuries to A.J. Green and DeAndre Hopkins, there are still lots of options for Arizona in the passing game with Rondale Moore, Christian Kirk, Zach Ertz and Chase Edmonds. Don't forget about Andy Isabella possibly getting to suit up if Green or Hopkins can’t go.
This is still the No. 3 offense in EPA/play and has the No. 4 success rate in the passing game. Last week’s loss showed us that Arizona does not like to go run-heavy and rushing for under 100 yards in the Week 5 meeting could also assure a more pass-heavy attack. Murray has become a much better pocket passer and is capable of putting up points against the 49ers who sit in the bottom-eight in pressure rate.
The 49ers seemed to be one of the more overrated teams this year as they are 2-5 ATS this season with their only SU wins coming against the Bears, Eagles, and Lions. They are 1-10 ATS at home in their last 11 games and relied on big plays to move the ball last week in Chicago. Yes, the 49ers will likely want to take a page out of the Packers’ playbook and run the ball against the weakness that is the Cards’ rush defense, but in the Week 5 meeting, QB Trey Lance had 89 of the team’s 152 rushing yards. San Francisco can’t also throw two solid backs at the Cards as the Packers did and RB Elijah Mitchell is dealing with a rib injury.
The Cardinals’ injuries may be more well-known, but the 49ers are banged up in some key areas, too. Deebo Samuel, who leads the team in every receiving stat and is averaging 117 yards per game is questionable with a calf injury and did not practice on Wednesday. Any missed production from him could be made up if George Kittle suits up Sunday — Kyle Shannahan expects him to dress. Mitchell, who has back-to-back 100-yards games, is still dealing with a rib injury that has him limited at practice this week but he should be good to go against the Cards’ soft run defense.
The 49ers’ defense could also be missing starters S Jimmie Wards and LB Azeez Al-Shaair. If Ward sits out, that could be a huge advantage for the Arizona passing game as the 49ers are a below-average team against the pass and could have four starting defensive backs that rank in the bottom half of the league, per Pro Football Focus. Safeties Ward and Jaquiski Tartt (Out) combined for 14 tackles in the Week 5 meeting and there is a possibility that both don’t suit up Sunday in what will likely be a pass-heavy Arizona offense.
Will Murray be limited Sunday if he suits up? For sure. But facing a pass rush that is struggling to get pressure and a secondary that could be without its best player, this Arizona offense can still move the ball. Getting this team, even with a bang-up Murray, at -1.5 is still a ride we’re willing to take. Arizona is 6-1-1 ATS versus the 49ers over the last eight meetings.
Under 46 (-110)
In the Week 5 meeting, the total closed at 48.5 and now sits below the key number of 47 at 46 in Week 9. That game finished with just 27 total points being scored and neither team gained more than 340 yards of total offense. Each team had one turnover and combined to score three TDs in five red zone trips. Penalties were costly, but it wasn’t like either team left a ton of points on the board that would've threatened this total.
The 49ers sit in 21st in offensive success rate while the Cardinals are the No. 4 team in the same statistic but have a ton of question marks offensively with the health of Murray, Green and Hopkins. San Francisco’s offensive advantage lies in the running game where the Cardinals sit 31st in yards per rush against at 4.9. San Francisco could be putting long, extended drives together if the Cards can’t slow down the run yet again.
Jimmy Garoppolo hasn’t been great since getting the starting QB job back. He hasn’t completed more than 17 passes in his two games and has just a single TD throw to his name. Last week’s yardage was skewed by a pair of long plays on short passes. Arizona holds opposing QBs to the fifth-lowest QB rating per game.
So many skilled players come into this game banged up with Murray, Green, Hopkins, Samuel, Kittle and Mitchell all drawing questionable tags. If they do suit up, the likelihood of them being at 100 percent is low. If any of these players are ruled out, we could start to see this total slip further south which shouldn’t take much since it already passed the key number of 47.
Protection could still be a problem for Murray as his offensive line is still littered with injuries. Starting center Rodney Hudson is questionable after being activated off the IR, while his backup, Max Garcia, is also questionable. The Cards had to start Sean Harlow at center last week which was his first start at the position ever and graded poorly in both the run and the pass. Murray has taken eight sacks over the last three games while the 49ers are a below-average QB pressure defense but do average 2.3 sacks per game.
We are halfway through the NFL season and injuries are starting to stack up. Both teams have a ton on the line in this divisional game and we like ball possession to be at a premium for both clubs. Fewer chances mean fewer points and we’re backing the Under 46 on Sunday.
Elijah Mitchell Under 68.5 rushing yards (-115)
Elijah Mitchell has back-to-back 100-yard games and now gets to see one of the NFL's worst run defenses Sunday in the Cardinals. Also in the favor of the 49ers is the health of Arizona QB Kyler Murray, who is questionable. If this Arizona offense struggles to move the ball, Kyle Shanahan’s offense could lean heavily on the run Sunday and wear down the Cards’ defense — much like the Packers did in Week 8.
However, what looks like a great matchup, may not actually be that way. Mitchell is dealing with a rib injury that has limited him this week as he participated in a non-contact jersey at practice. RB Jeff Wilson has also been activated this weekend, which will likely cut into Mitchell’s snaps.
With a rushing total on the high side at 68.5 (the same as Jonathan Taylor’s Week 9 rushing total), there are too many red flags here for us to hit the Over. An in-game injury is not worth the risk on the Over but well worth it for the Under.
Arizona will want to tighten things up on defense after getting embarrassed by A.J. Dillon and Aaron Jones last week and Kliff Kinsbury will likely want to try and make Jimmy G beat him through the air.
Injuries and a high total have us hitting the Under on Mitchell’s rushing total despite the great matchup.