Chargers vs. 49ers Prediction, Odds & Expert Picks: NFL Preseason Week 3
The penultimate game of the preseason sees two California teams collide, and my Chargers vs. 49ers prediction sees Los Angeles leaving Levi's Stadium with a victory.
Kickoff is set for 8:30 p.m. ET (NFL+) from Levi's Stadium in Santa Clara, Calif. The best sports betting sites list the Chargers as -115 betting favorites.
As we continue our NFL preseason Week 3 predictions, remember that the preseason is less about winning and more about player development and evaluation - so size your bets accordingly.
🏈 Chargers vs. 49ers prediction & expert picks
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✅ Against the spread pick: Chargers -1.5 (-102 via FanDuel) ⭐⭐
✅ My best bet: Chargers First Half -0.5 (-105 via Betway) ⭐⭐⭐
📊 Chargers vs. 49ers odds
Live updated odds from our best live betting sites. Follow the latest NFL scores for line history and matchup info.
🪧 Chargers vs. 49ers opening odds:
- Chargers: -2.5 (-108)
- 49ers: +2.5 (-112)
🔮 Chargers vs. 49ers ATS prediction
⚡️ Chargers -1.5 ⭐⭐
📊 Best odds: -102 via FanDuel ($10 to win $9.80)
🔢 Implied probability: 50.50%
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The Chargers aren’t expected to deploy their starters, so we’re likely going to see a healthy amount of Trey Lance. That may be good in this spot. Lance - who was drafted by the 49ers in the first round of the 2021 NFL Draft - now gets a chance to somewhat settle the score.
The injury-riddled 49ers are also not expected to feature starters. Behind Purdy are banged-up Mac Jones, Carter Bradley, and Nate Sudfeld, who the team just signed this week as it navigates the depletions to the quarterback room. While Sudfeld is no stranger to San Francisco, it’s a concerning sign for the 49ers’ depth.
The Chargers may not care about winning this game, but Lance certainly does.
He told reporters after last week’s defeat that he wants to go out and win against his former team. That isn’t much of an edge, but it is enough of one for me to have some confidence in the Chargers, and it helps that San Francisco’s roster is so banged up.
📖 Check out our 2025 NFL preseason betting guide for the best betting strategies and full NFL preseason schedule.
💰 Chargers vs. 49ers best bet
1️⃣ Chargers First Half -0.5 ⭐⭐⭐
📊 Best odds: -105 via Betway ($10 to win $9.52)
🔢 Implied probability: 51.22%
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The reasoning for this bet is essentially the same as for the last, but we specifically want to minimize the risk of bad possessions from Los Angeles’ final quarterback, DJ Uiagalelei. The former Clemson, Oregon State, and Florida State starter appeared in just five games for the Seminoles last year and completed 53.8% of his passes with four touchdowns and six interceptions.
Uiagalelei hasn’t been bad in the preseason, but offensive coordinator Greg Roman doesn’t ask very much of him as a passer – in five drives, Uiagalelei has attempted four passes. Uiagalelei’s drives all came deep into games, well into the second half, with Roman refusing to give him the ball until the fourth quarter.
We would rather take our chances with Lance and Taylor Heinicke than the full Los Angeles quarterback room. With both Purdy and Jones unlikely to play, the Chargers tandem we’re likely to see in the first half has a huge leg up – both in experience and motivation – over the counterparts we’re likely to see from the 49ers.
🚑 Chargers vs. 49ers injuries
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