Cardinals vs. Chargers Prediction, Spread, NFL Week 1 Picks – Sunday, September 13

Cardinals vs. Chargers is set for kickoff at 4:25 p.m. ET on Sunday, September 13, with the Chargers being 9.5-point favorites, via PrizePicks.

After posting a 3-14 record last year, the Cardinals are expected to be one of the worst teams in the NFL this season. The Chargers look to build on their 11-6 record in 2025 that culminated with a disappointing 16-3 loss to the Patriots in the Wild Card round.

Below, we’ll break down our Cardinals vs. Chargers prediction and picks for NFL Week 1, including the spread, over/under, and key player picks for PrizePicks.

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Cardinals vs. Chargers Prediction, Spread, Over/Under for Week 1 – Sunday, September 13

Injuries were a problem for the Chargers last season, especially across their offensive line. The defense helped pick up the slack, allowing the ninth-fewest points per game (20.0) in the NFL. According to RBSDM, they ranked seventh in dropback EPA allowed and fourth in rush EPA allowed.

Defense was not the forte of the Cardinals last season. They gave up 28.7 points per game and finished tied for the third-fewest sacks (30). Their porous defense contributed to their -133 point differential.

Cardinals vs. Chargers Spread, Over/Under for Week 1 – Sunday, September 13

The Chargers enter Sunday’s game as a 9.5-point home favorite against the Cardinals, via PrizePicks Team Picks.

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PrizePicks data is live as of writing and is subject to change.

Cardinals vs. Chargers Prediction on Over/Under – Sunday, September 13

Here are the key game stats and trends behind our Cardinals vs. Chargers prediction on the over/under for Sunday, September 13.

• The Chargers already lost C Tyler Biadasz (knee) for the season, but OTs Rashawn Slater and Joe Alt will be available for Week 1. Slater sat out all of last season, while Alt was limited to six games.
• Los Angeles added one of the best offensive minds in football when it named former Dolphins head coach Mike McDaniel as its offensive coordinator this year.
• The Cardinals were 26th in dropback EPA allowed and 22nd in rush EPA allowed a season ago.
• Cardinals QB Jacoby Brissett recorded at least 2 TDs in 10 of his 12 starts last year.
• Brissett will have his top pass-catchers available with TE Trey McBride, WR Marvin Harrison Jr., and WR Michael Wilson all healthy.

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Cardinals vs. Chargers Picks, Player Stats for PrizePicks in Week 1: 9/13/26

Here are top Cardinals vs. Chargers picks to target on PrizePicks for Sunday, September 13. Week 1 NFL picks for PrizePicks include Chargers WR Ladd McConkey and Cardinals QB Jacoby Brissett.

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Cardinals QB Jacoby Brissett vs. Chargers: 34.5 Pass Attempts

• Since their defense struggled to keep teams out of the end zone, the Cardinals needed to throw a lot to try and keep pace last year. They led the NFL in pass attempts (649) and were last in rush attempts (366).
• Brissett logged at least 35 pass attempts in nine of his 12 starts. In seven of them, he attempted at least 40 passes.
• Despite his hefty workload, the veteran quarterback had only 8 INTs to go along with his 23 TDs
• Arizona selected RB Jeremiyah Love with the #3 in the 2026 Draft, but he is dealing with an ankle injury. He is officially listed as questionable, and Cardinals head coach Mike LaFleur said he is “trending well.” Even if he does take the field, his workload could be limited.

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Chargers WR Ladd McConkey vs. Cardinals: 58.5 Receiving Yards

• The addition of WR Keenan Allen resulted in McConkey’s target share dropping from 23.3% in 2024 to 19.2% last year.
• While McConkey wasn’t targeted as much, he was 10th among qualified wide receivers in routes run, per Pro Football Focus.
• With Allen now a member of the Colts, the third-year receiver is positioned to lead the Chargers in target share again.
• As the top option for Los Angeles in 2024, McConkey finished with 1,149 receiving yards in 16 games. In nine of those matchups, he registered at least 60 receiving yards.
• Per RotoWire, the Cardinals allowed the ninth-highest catch rate (63.8%) to wide receivers last year.

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Make Cardinals vs. Chargers Picks on PrizePicks

We have the potential for a high-scoring matchup when the Chargers host the Cardinals in Week 1. Potentially the top wide receiver on the depth chart once again, Ladd McConkey seems primed for increased production. With the Cardinals expected to struggle on defense yet again, Brissett should be asked to throw a lot as Arizona tries to keep pace with Los Angeles.

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