The San Francisco 49ers and Los Angeles Chargers will face off in Week 2 of the NFL preseason tonight. Kickoff is set for 10:00 p.m. ET from SoFi Stadium in Inglewood, Calif. The game will broadcast live on NFL Network.
The 49ers are favored by -1.5 with the over/under set at 38.5 total points. The 49ers are 53¢ favorites to win outright, while the Chargers are 49¢ underdogs.
Let's get into my 49ers vs Chargers predictions and NFL picks for Thursday, August 20.
My 49ers vs Chargers Prediction
- 49ers vs Chargers pick: Chargers to Win (48%, Polymarket)
My 49ers vs Chargers pick is on Los Angeles to win, currently available at 48% on Polymarket. But as always, make sure to find the best odds by checking our live NFL odds page.
49ers vs Chargers Odds
49ers vs Chargers NFL Preseason Preview
Kyle Shanahan and Brock Purdy were both vocal in proclaiming their displeasure regarding their performance in joint practices against the Chargers this week. Shanahan even went on to say he “didn’t really like how we finished the day.”
As I read between the tea leaves of both their comments, it seems that, beyond the first teams on both sides of the ball, the 49ers are struggling to identify reliable depth pieces.
Purdy is slated to get the start in this game, but I do not factor that much into the handicap of this preseason clash with the Chargers for two reasons.
First, the health of the star players for the 49ers continues to be an issue — meaning even in the short stint Purdy will be on the field, he’ll be tasked with moving the ball without the likes of Mike Evans, Christian McCaffrey and George Kittle.
Second, Los Angeles also plans to play Justin Herbert and the starting offense for a series or two. This should neutralize any advantage for either team, given the very small sample size we will have to see the well-known regular-season contributors.
It is always difficult to project which defensive starters will play and how long they will remain in the game, but one key cog for the Niners, Nick Bosa, will almost certainly be resting on the sidelines.
We must rely on reports from joint practices and last week’s preseason showing to project how each defense may perform in this game.
Vic Tafur of the Athletic covered the joint practices between these two teams, and he made it quite clear in an article this week that outside of defensive tackle Osa Odighizuwa’s disruption, the San Francisco defense was the less physical team of the two and surrendered a number of big plays.
This is right in line with what we witnessed against the Titans in the 49ers' first preseason game, specifically, in terms of stopping the run. The Titans averaged 5.4 yards per rush against the Niners, while the Shanahan-led offense could only muster 3 yards per carry on 28 carries. Simply put, the 49ers lost the line of scrimmage in their 19-13 defeat.
The Chargers, on the other hand, turned in an impressive, well-rounded account of their depth in a 27-7 win in Houston.
Despite facing the experienced Davis Mills, the Chargers limited the Texans offense to just 5.5 yards per pass attempt on 15 passes while Mills was under center. For the game’s entirety, Houston converted just 33% of 3rd-down attempts.
The Chargers were both efficient and explosive in their first outing under new offensive coordinator Mike McDaniel. They converted 50% of the 3rd-down attempts and averaged 9.5 yards per pass attempt.
McDaniel orchestrated six chunk gains of 15+ yards through the air, including a 32- and 55-yard completion from 3rd-string quarterback DJ Uiagalelei.
Herbert’s direct backup, Trey Lance, had an up-and-down performance but continued to show flashes of what made him a high draft selection just a few years ago.
It’s worth noting that in the 2025 preseason for the Chargers, Lance was a reliable performer, accounting for 415 total yards and three touchdowns without committing a turnover.
49ers vs Chargers Prediction, Betting Analysis
Without reading too much into one exhibition game, the Chargers felt like an operation primed for success from top to bottom. They averaged 6.3 yards per play while limiting Houston to just 4 yards per play and 209 total yards for the entire game.
Given that the 49ers’ main objective for Thursday’s game might be to focus on fundamentals and keep many of their players in bubble wrap, I do not understand why they are favored in this spot.
The Chargers under Jim Harbaugh have scored 23 or more points in five consecutive preseason games. Kyle Shanahan’s Niners have reached that number just once in their last seven exhibition matchups.
In addition to Los Angeles seemingly having the more reliable depth, I will gladly back the team placing more emphasis on success in these games by taking the Chargers at 48% to win this game on Polymarket.
Trade: Chargers to Win (48%, Polymarket)
