Week 2 of the NFL preseason has arrived with a doubleheader on Thursday, August 20. Following the Raiders vs. Texans kicking off at 8:00 p.m. ET, the 49ers vs. Chargers wrap up the schedule with a 10:00 p.m. ET kickoff on NFL Network.
San Francisco opened the preseason with a 19-13 loss vs. the Titans last week, while the Chargers rolled to a 27-7 win over the Texans. Both teams are expected to feature starters in some capacity on Thursday, leading to a "pick 'em," with the 49ers featuring a 1.85x payout to win compared to the Chargers’ 1.88x payout if they win, per PrizePicks Team Picks.
Below, we’ll break down our 49ers vs. Chargers prediction, featuring the spread and over/under, followed by NFL preseason picks for player projections on PrizePicks.
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49ers vs. Chargers Prediction, Spread, Over/Under for NFL Preseason – Thursday, August 20
The 49ers elected to rest projected starters to open the preseason, but head coach Kyle Shanahan discussed a different plan for Thursday: “I expect a number of starters to play, unlike last week.”
Keep in mind several key San Francisco pieces, including RB Christian McCaffrey, WR Mike Evans (quad), and EDGE Nick Bosa (knee), carry a questionable status. Plus, TE George Kittle continues to recover from his Achilles injury.
Los Angeles is also expected to feature starters for one series, meaning QB Justin Herbert will orchestrate offensive coordinator Mike McDaniel’s offense for the first time in a game.
With that said, neither team is given a big edge tonight, as the 49ers are favored by 1.5 points. Here are the full payouts for the 49ers vs. Chargers NFL preseason game on PrizePicks.
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49ers vs. Chargers Prediction on Winner for NFL Preseason – 8/20/26
Here are the key game stats and trends behind our 49ers vs. Chargers prediction on the winner for Thursday’s NFL preseason game.
- When asked if 49ers QB Brocky Purdy would play, Shanahan said, “Haven’t told him yet, but there’s a good chance.” If that’s the case, San Francisco would match the Chargers, featuring QB Justin Herbert.
- Los Angeles could feature struggles on offense due to a new system. Meanwhile, Purdy has operated Shanahan’s offense as a full-time starter since 2023.
- Chargers C Tyler Biadasz suffered a major knee injury this week, while OT Rashawn Slater has recently missed practice due to a “minor flare-up” in his knee. Los Angeles’ usual offensive line problems are already in mid-season form, potentially impacting the efficiency of its offense—whether it’s the starters or backups.
- Purdy is likely in line for one series, suggesting QB Mac Jones may get the most work in the QB room. Third-string 49ers QB Kurtis Rourke recently suffered a broken rib, providing fourth-string QB Adrian Martinez with more snaps.
- If Jones is limited with few snaps, the Chargers would likely have the leg up thanks to second-string QB Trey Lance and third-string QB DJ Uiagalelei.
Lock in your 49ers vs. Chargers prediction on PrizePicks before tonight’s NFL preseason game.
49ers vs. Chargers Picks, Player Stats for NFL Preseason on PrizePicks: 8/20/26
Check out some of our top 49ers vs. Chargers picks to target, featuring WR De’Zhaun Stribling, RB Kimani Vidal, and QB Justin Herbert.
49ers WR De’Zhaun Stribling vs. Chargers: 19.5 Receiving Yards
- Rookie WR De’Zhaun Stribling has quickly drawn praise throughout the offseason, totaling 7 catches for 62 receiving yards in NFL preseason Week 1.
- Stribling was able to accomplish this in a limited role, taking only 22 snaps. He finished with 8 targets in 17 pass snaps, showcasing his ability to dominate the workload.
- If Stribling lines up with the starters tonight, he benefits from Purdy throwing the ball, followed by Jones. Solid QB play certainly aids his chance for stacking yards.
- Furthermore, the 49ers’ receiving unit is beat up, as WR Mike Evans (knee) and WR Christian Kirk (calf) could each sit out tonight. Of course, WR Ricky Pearsall (knee) has already been declared out for the season, too. Stribling should continue to enjoy plenty of targets during the preseason.
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Chargers RB Kimani Vidal vs. 49ers: 18.5 Rush Yards
- As mentioned, the Chargers are expected to feature offensive starters for one series. That may lead to snaps for RB Omarion Hampton, but he’s projected only 14.5 rushing yards tonight. And that’s a Demon projection, meaning users can only select More—a lower probability but higher reward if you’re right.
- Behind Hampton, there’s an ongoing battle for the RB2 role between Kimani Vidal and Keaton Mitchell.
- In NFL Preseason Week 1, Vidal logged 14 snaps, while Mitchell rested. The Bolts’ unofficial depth chart listed Mitchell OR Vidal as the second-string back, but Mitchell resting alongside Hampton last week suggests he could be ahead of Vidal.
- With that said, Mitchell could be in line for more work tonight—especially since he was absent a week ago. That would likely lead to a drop in touches for Vidal.
- Furthermore, Vidal struggled in his first preseason appearance by logging 8 rushing yards on 5 carries (1.6 yards per rushing attempt).
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Chargers QB Justin Herbert vs. 49ers: 27.5 Pass Yards
- Herbert will make his preseason debut tonight, headlining McDaniel’s offense for the first time.
- As mentioned, featuring in a new offense could lead to initial growing pains. Furthermore, Los Angeles is rapidly approaching an injury-riddled offensive line, likely harming Herbert’s chance for a clean pocket.
- If Herbert is regularly under pressure tonight, that should lead to fewer snaps as well, with the Chargers looking to protect their franchise QB ahead of the regular season.
- He made one preseason appearance with 8 snaps and 46 passing yards in 2025. However, he accomplished this on only 5 passing attempts and 2 completions. Repeating 23.0 yards per completion is far from reliable.
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Make 49ers vs. Chargers Picks on PrizePicks
While each team deals with injuries in the starting lineup, the 49ers and Chargers are expected to feature first strings in tonight’s preseason game. However, this is only expected to last for about one series, opening up opportunities for players fighting for snaps—including De’Zhaun Stribling and Kimani Vidal.
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