Chargers vs. 49ers Prediction, Odds, Spread, Trends for NFL Preseason Week 3

Iain MacMillan | Aug 23, 2025

Trey Lance will face his former team, the San Francisco 49ers. / Kirby Lee-Imagn Images

We've reached the final day of NFL Preseason action, and one of the top storylines will take place in the prime time showdown between the Los Angeles Chargers and San Francisco 49ers.

Trey Lance, the former No. 3 overall pick, will face his former team, the San Francisco 49ers. Justin Herbert is unlikely to see the field, leaving Lance to take the majority of snaps. Expect the 49ers to keep their starters sidelined as well. Mac Jones has a chance to play the most snaps at quarterback.

Let's dive into the odds and my best bet for this exhibition matchup.

Chargers vs. 49ers Odds, Spread, and Total

Odds via FanDuel Sportsbook

Spread

• Chargers -1.5 (-102)
• 49ers +1.5 (-120)

Moneyline

• Chargers -118
• 49ers +100

Total

• OVER 35.5 (-115)
• UNDER 35.5 (-105)

Chargers vs. 49ers How to Watch

• Date: Saturday, August 23
• Time: 8:30 p.m. ET
• Venue: Levi's Stadium
• How to Watch (TV): ESPN Unlmtd
• Chargers Record: 2-1
• 49ers Record: 1-1

Chargers vs. 49ers Betting Trends

• Jim Harbaugh is 13-9 straight up and 13-9 against the spread in the preseason in his career
• Kyle Shanahan is 13-12-1 straight up and 14-11-1 against the spread in the preseason in his career

Chargers vs. 49ers Prediction and Pick

I'm going to back the Chargers as slight favorites in this one. Trey Lance has been fantastic in the preseason so far, completing 27-of-49 passes for 296 yards and two touchdowns. Mac Jones, on the other hand, has thrown for 209 yards and two interceptions with no touchdowns. Lance has also racked up 81 yards and a touchdown on the ground.

No one will be more motivated than Lance, who will be playing against the team that drafted him No. 3 overall and then quickly moved on from him.

Jim Harbaugh has also been strong in the preseason as a head coach, going 13-9 against the spread. That's enough for him to trust the Chargers in this spot.

Pick: Chargers -1.5 (-102) via FanDuel

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