49ers vs Cardinals Predictions Week 5 | NFL Pick of the Day

Last Updated: Oct 8, 2021

The NFC West is always one of the more competitive divisions in the NFL, and this 2021 season is no different. The Arizona Cardinals sit in first place right now at 4-0, led by Kyler Murray who is playing fantastic football.

On the other hand, the San Francisco 49ers are currently in last place despite sitting at 2-2 and still looking like a competitive and potential playoff team.

San Francisco is in a tough spot this week, coming off a tough loss to the division rival Seattle Seahawks at home. This one came just after they lost at home to the Green Bay Packers in Week 2.

Two tough losses in a row at home and now they have to fly to Arizona to take on the undefeated Cardinals. Not ideal.

With that said, let’s dive right in the NFL pick of the day series, featuring the 49ers and Cardinals.

Please note that all 49ers vs Cardinals odds and lines are current as of Friday, October 8.

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49ers vs Cardinals Prediction

After starting off the season 2-0, falling to 2-3 would be a worst-case scenario type of spot for the 49ers to be in. The Cardinals will come out firing in this one as they’re sitting undefeated coming off a huge division win against the Rams.

It’s always exciting when these division rivals go at it, and I expect this to be another exciting one that could come down to the wire.

As of now, it looks like Jimmy Garoppolo will either play through injury or be sidelined, meaning we could see what Trey Lance is capable of when he gets a whole game to himself as the starter.

Lance came in last week when Garoppolo hurt his calf, going 9/18 for 157 yards and two touchdowns. He also added 41 rushing yards on seven carries, adding a dynamic to the offense that’s missing when Garoppolo is under center.

Deebo Samuel is playing like one of the best wide receivers in the NFL right now, and everyone is just itching to see George Kittle get going. The tight end saw 11 targets in Week 4 — his largest volume this season — which should help boost this San Francisco offense.

The biggest area that the Cardinals lack in is their rush defense, as they currently give up 135.8 rushing yards per game — the sixth-worst mark in the NFL. The 49ers have dealt with all sorts of injuries to their running backs and will come out with a committee approach per usual.

None of these running backs has shown anything overly impressive this year, though rookies Trey Sermon and Elijah Mitchell have shown signs of promise. One of the few good things about the 49ers last week was Sermon, so it’ll be interesting to see if they get him going. This Cardinals defense can be run on, and I expect it’ll happen a decent amount here.

For Arizona, Murray is averaging over 300 passing yards per game this year, and this Cardinals team has put up at least 30 points each week. DeAndre Hopkins has been off to a bit of a slow start, but we’ve seen guys like Christian Kirk, AJ Green, and rookie Rondale Moore all get involved.

Murray is doing a great job of spreading the ball around and this offense has been on fire. I’m taking the Cardinals 30-24 in a fairly high-scoring matchup here.

Prediction: Cardinals 30, 49ers 24

DeAndre Hopkins, WR, Arizona Cardinals

Although he’s gotten off to a bit of a slow start, DeAndre Hopkins and the Arizona Cardinals are off to a 4-0 start and are the lone remaining undefeated team in the NFL. (Image: USA TODAY Sports)

49ers vs Cardinals Best Bets

Best Bet: Total Over 49 points (-110) at Caesars

The best odds you can get right now on the total points is at Caesars, as the 49-point total sits at (-110). Both of these offenses can put up points and both teams have had their share of high-scoring matchups this year.

The 49ers have given up 58 points over the past two weeks and had a total of 74 points in Week 1, as they beat the Lions 41-33. Outside of Week 2 against the Eagles, they’ve had nothing but high-scoring matchups and have a game total of 49 or more in their other three games.

Not much needs to be said regarding the Cardinals given the way that Murray and this team have been playing. I fully expect this one to be a shootout and am taking the over on the points, making this our NFL bet of the day.

Best Bet: Cardinals -5 (-110) at BetMGM

The Cardinals have scored 31 points or more in every single game this year. They average 35 per game, which is the highest in the NFL.

The 49ers have looked solid, and despite losing a couple of tough games, could easily be 3-1 right now — something that’s reflected in the NFL gameday odds.

Losing two tough ones in a row, Garoppolo dealing with his calf injury, and now traveling to Arizona to take on an undefeated Cardinals team is not how the 49ers wanted this year to start out. I’ve got the Cardinals winning by six in this one and could easily see them winning by a touchdown or more.

The current moods of these two teams are almost polar opposites and I don’t see the 49ers turning things around this week. They’ll keep it close and it should be an exciting matchup, but with the way this Arizona team is playing, I’m expecting them to cover this one.

Thank you for reading our 49ers vs Cardinals predictions. Consider checking out our NFL Week 5 Best Bets and NFL Week 5 Parlays Picks for more Week 5 tipster picks.


Aaron Schill

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