Los Angeles Chargers vs San Francisco 49ers Point Spread Picks

Los Angeles coach Jim Harbaugh is 13-9 in the preseason. He has a 2-1 record this preseason and is a combined 8-1 in Weeks 3 and 4. The offense has averaged 27.25 points in its last four August contests. Chargers QB Trey Lance has played well and has been motivated, the third overall pick in the 2021 NFL draft. Speaking of motivation, he's facing the team that drafted and gave up on him in this one. The San Francisco defense has given up 30 and 19 points in two games. The 49ers gave up 30 points in their only preseason home game in 2025, a loss to Denver, surrendering 368 yards (153 rushing). Play Los Angeles + OVER the total. 

Los Angeles has won two of three with the defense playing great in a 19-16 win over Denver and last week's 20-17 at Atlanta. The Chargers are 21-6 UNDER the total after allowing 150+ rushing yards in the last game. San Francisco will attack that run defense as they're a ball control offense under Kyle Shanahan that aims to grind out first downs and chew up the clock, ranked No. 12 in time of possession. In the previous three years, they ranked No. 5, No. 6, and No. 17 in that category. The 49ers are currently No. 1 defensively in total yards allowed and against the run, eighth against the pass, plus seventh with 22 sacks. Chargers QB Justin Herbert's stats (13 TDs, 5 INTs) have been down because of injuries to the downfield passing attack with WRs Keenan Allen and Mike Williams hurting. Williams (ankle) is likely out again while Allen (hamstring) has only played in two games and missed practice this week. Herbert has gone four consecutive games without going over 300 yards and has failed to hit a pass over 20 yards in the last three. And in a game involving NFL teams that average 18-23 points eight contests into the season, the UNDER is 112-64 when the total is between 42.5 and 49. Take Los Angeles/San Francisco UNDER the total.

San Francisco has high hopes for rookie quarterback Trey Lance, and he did throw an 80-yard TD pass in the 49ers' 19-16 loss to Kansas City. His final numbers, though, were not as impressive as he completed just 5 of 14 for 128 yards with a TD and no interceptions. Josh Rosen went 10 of 15 for 93 yards and is a capable backup if he can stay healthy for a change. Starter Jimmy Garoppolo completed all three of his passes for 26 yards. The Niners racked up 175 rushing yards, led by JaMycal Hasty with 63. The Chargers edged the Rams, 13-6, with Chase Daniel throwing for 104 yards on 15 of 24. Easton Stick also went 7 of 7 for 63 yards. Los Angeles had an opening drive that was 21 plays, but the Chargers managed only a field goal against mostly reserves on the Rams defense. The teams met in the final 2019 preseason game, and the game went OVER by 17 points as San Francisco won three of four in the preseason. Justin Herbert has been ruled out of the preseason by first-year coach Brandon Staley, and Lance will get every opportunity to overtake Garoppolo for the starting role. Look for the rookie to put up better numbers this week. Take the 49ers for a Max Play and the OVER.

San Francisco has won and covered all three games while the Chargers have lost all three with a 0-2-1 ATS record.  Also, the 49ers remember a tough 29-27 loss to the Chargers last September and coach Kyle Shanahan is now 6-4-1 ATS in his two preseasons with the 49ers. San Francisco got a good showing from Jimmy Garoppolo as he went 14-of-20 for 188 yards and a touchdown and he played the entire first half in a 27-17 win over Kansas City. Nick Mullens finished 8-of-11 for 84 yards and the Niners outgained the Chiefs 381-248. The Chargers, obviously, can't wait for the regular season to start as they have shown little interest in preseason games and coach Anthony Lynn is 3-8 in 11 preseason games. Easton Stick was 12-of-16 for 82 yards with a touchdown in the Chargers' 23-15 loss to Seattle.  Tyrod Taylor was 6-of-9 for 61 yards and actually led the Chargers in rushing with 34 yards. These teams played in the 2018 preseason finale and the game went OVER by 9.5 points. Garoppolo possibly could get more playing time in this game. Play the 49ers and the OVER.