Predicting Chargers' Starters vs Bills for NFL Week 3: Multiple Starters Out

The banged-up Chargers head to Western New York to take on the Buffalo Bills with their season potentially on the line. See which starters are out for Week 3.

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers edge rushers Khalil Mack (52), Akheem Mesidor (90) and Tuli Tuipulotu (45) react after a play against the Las Vegas Raiders during the first half at SoFi Stadium. Mandatory Credit: Kirby Lee-Imagn Images | IMAGN IMAGES via Reuters Connect

It is only Week three and the Chargers are already running out of injured reserve slots. Head coach Jim Harbaugh redesigned the offseason program and ran a lighter training camp in an apparent attempt to make it to the season as healthy as possible. The week three injury report is long and impactful.

Los Angeles will take on the Buffalo Bills this Sunday in Western New York and their season may be on the line after falling to 0-2. They will have multiple changes to their starting lineup due to injuries, lets dive into the changes.

Chargers offense

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers wide receiver Ladd McConkey (15) celebrates with tight end Oronde Gadsden (86) after a touchdown against the Las Vegas Raiders during the second half at SoFi Stadium. Mandatory Credit: Gary A. Vasquez-Imagn Images | IMAGN IMAGES via Reuters Connect

Quarterback: Justin Herbert
Running back: Omarion Hampton
Fullback: Alec Ingold
Tight end: Oronde Gadsden II
Wide receiver: Ladd McConkey
Wide receiver: Quentin Johnston
Left tackle: Rashawn Slater
Left guard: Trevor Penning
Center: Jake Slaughter (R)
Right guard: Cole Strange
Right tackle: Joe Alt

The Chargers lost both of their top tight ends in week two against the Raiders. Oronde Gadsden will assume starting duties and recently signed newcomer Hayden Rucci will be the backup, with Patrick Herbert set to be elevated and active from the practice squad.

Los Angeles is now down to their fifth option at left guard. Branson Taylor started the season on injured reserve, Jake Slaughter moved over to assume the starting center duties, Trey Pipkins has not practiced in two weeks with a knee injury and was just placed on IR and starter Kayode Awosika will miss at least this week with what is labeled a fibula injury. Trevor Penning who served as the swing guard in week two, will make his debut in 2026 as a starter and assume the left guard role.

Wide receiver Ladd McConkey will have to monitor his ribs but he practiced in full all week and should be good to go as an important offensive weapon for quarterback Justin Herbert. Wide receiver Brenen Thompson is out for this game and should make way for the debut for veteran journeyman wide receiver Marquez Valdez-Scantling.

Chargers Defense

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers edge rusher Khalil Mack (52) is introduced prior to the game against the Las Vegas Raiders at SoFi Stadium. Mandatory Credit: Gary A. Vasquez-Imagn Images | IMAGN IMAGES via Reuters Connect

Edge rusher: Khalil Mack
Edge rusher: Tuli Tuipulotu/ Akheem Mesidor
Defensive tackle: Teair Tart
Defensive tackle: Jamaree Caldwell
Linebacker: Daiyan Henley
Linebacker: Del'Shawn Phillips
Nickelback: Derwin James Jr
Safety: Tony Jefferson
Safety: RJ Mickens
Cornerback: Tarheeb Still
Cornerback: Cam Hart

The Chargers will have a few shakeups on defense with injuries hitting this side of the ball as well. Most notably, starting defensive tackle Dalvin Tomlinson is out this week with a hamstring injury. Jamaree Caldwell will get extra reps this week as the starter opposite of Teair Tart and rookie Nick Barrett will also see an elevated role.

Edge rusher Tuli Tuipulotu was nursing a hamstring injury this week but was upgraded to a full participant on Friday. Rookie Akheem Mesidor may see extra snaps if Tuipulotu needs to manage his hamstring.

Last week, RJ Mickens got the start opposite Tony Jefferson with Elijah Molden still out with a hamstring injury and that should continue. Expect to see plenty of rookie Genesis Smith though with the Bills having a preference to attack downfield.