Week 1 · Sunday, September 13 · 4:25 PM ET
Why This Game Matters
This is about as lopsided as a Week 1 slate gets on paper: a Chargers team coming off back-to-back playoff berths and debuting Mike McDaniel's rebuilt offense hosts a Cardinals team that just finished 3-14, fired its coach, released its franchise quarterback, and enters with the league's lowest projected win total. For Arizona, it's Mike LaFleur's coaching debut and Jacoby Brissett's first start as the presumptive starter; for LA, it's the first live test of whether a healthy offensive line and a new scheme can finally get Justin Herbert over the playoff hump. A blowout early would set the tone for two very different seasons.
Real Player Matchups
- ARI pass rusher Josh Sweat (12.0 sacks, 17 QB hits in 2025) vs. a LAC offensive line that allowed 60 sacks last season.
- LAC pass rusher Tuli Tuipulotu (13.0 sacks, 23 QB hits in 2025) vs. a ARI offensive line that allowed 59 sacks last season.
- ARI's Trey McBride drew a 27% target share in 2025 (+73 receiving EPA) against a LAC defense ranked #7 of 32 in EPA allowed.
Real 2025 season production (nflverse), a prior-season baseline pending real 2026 games.
Key Matchups
- Jacoby Brissett's first start as Arizona's QB1 against a Chargers pass rush featuring Khalil Mack (13th season) and reigning Pro Bowler Tuli Tuipulotu
- Mike McDaniel's offensive debut as Chargers OC, with Justin Herbert working behind healthy tackles Rashawn Slater and Joe Alt but an unsettled center spot after Tyler Biadasz's knee injury
- Omarion Hampton's first game as the Chargers' unquestioned lead back, stepping into the role after Najee Harris departed in free agency
- Whether No. 3 overall pick Jeremiyah Love (high ankle sprain) is healthy enough to debut for Arizona, and how a rebuilt Cardinals roster holds up after a 2025 season that ended with nine straight losses
Injury Report
Jeremiyah Love · ARI RB
Out (preseason)
Suffered a high ankle sprain in his preseason debut against the Raiders; considered unlikely to play again in the preseason, though the team is hopeful he can return for the Week 1 opener.
Tip Reiman · ARI TE
PUP
Opened training camp on the PUP list with a foot injury; head coach Mike LaFleur has said he won't be ready for Week 1.
Josh Sweat · ARI OLB
PUP
Opened training camp on the PUP list with a knee issue described as maintenance-related; coaches have expressed confidence he'll be ready for Week 1.
Tyler Biadasz · LAC C
Out (indefinite)
Carted off with a left leg/knee injury during an Aug. 18 joint practice with the 49ers; reported to include structural knee damage.
Rashawn Slater · LAC OT
Healthy
Cleared for camp after missing all of 2025 with a torn patellar tendon suffered in early August of last year.
Series History
All-time: Chargers lead the all-time series 11-5 across 16 meetings (regular season only; the two franchises have never met in the playoffs), with Los Angeles holding a 407-318 scoring edge.
Last meeting: The teams last met on Oct. 21, 2024, a Monday Night Football game in Arizona during Jim Harbaugh's first season as Chargers head coach. The Cardinals won 17-15 on a Chad Ryland field goal as time expired.
- · The Cardinals and Chargers have never faced each other in the postseason.
- · As teams in different conferences, they meet only about once every four years under the NFL's rotating scheduling formula, so this Week 1 date is a relatively rare crossing.
Weather
SoFi Stadium in Los Angeles has a fixed roof — weather is not a factor for this game.
Records & Rankings on the Line
- · Chargers enter at No. 15 in the power rankings off an 11-6, playoff 2025 season; Cardinals sit dead last at No. 32 with the NFL's lowest projected win total (around 3.5) entering 2026.
- · Arizona is trying to snap a nine-game losing streak that closed out the 2025 season under a brand-new coaching staff.
- · Los Angeles fell 16-3 to the eventual AFC champion Patriots in the 2025 Wild Card round; the McDaniel-led offense is the team's answer for closing that gap, starting with Week 1.
The Desk Weighs In
Duke Callahan
LAC -10
Reasoning not yet published for this pick.
Vega Okafor
LAC -13
"The efficiency numbers are the one part of this game that doesn't fully back the number I'm giving you — Arizona's offense actually grades out ahead of the Chargers' by 2025 EPA. I'm still on LA because that was the old coordinator's offense, not Mike McDaniel's. A new play-caller makes last year's data the least reliable input on the board this week."
Sunny Marchetti
LAC -10
Reasoning not yet published for this pick.
Reese Thackeray
LAC -9
Reasoning not yet published for this pick.
Priest Dunbar
LAC -8
Reasoning not yet published for this pick.