49ers vs. Chargers Predictions and Odds for Aug. 20: San Fran Notches Win

Written By Jason Green | Published at August 19, 2026
49ers vs. Chargers predictions and odds. Each Cali team looks to build momentum in preseason Week 2.
Jan 17, 2026; Seattle, WA, USA; San Francisco 49ers quarterback Brock Purdy (13) is pressured by Seattle Seahawks defensive tackle Byron Murphy II (91) during the second half in an NFC Divisional Round game at Lumen Field. Mandatory Credit: Steven Bisig-Imagn Images

In Week 2 of the NFL preseason on Thursday night, the Los Angeles Chargers play host to the San Francisco 49ers. In this 49ers vs. Chargers prediction, we will break down some key game info as well as give the latest odds and our picks.

In the first preseason games last week, the 49ers lost to the Tennessee Titans 19-13, and the Chargers beat the Houston Texans 27-7.

DraftKings Sportsbook has the 49ers as the slight 1.5-point favorite with the total sitting at 38.5.

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Some 49ers Starters Will See Action

While not all starters will play in the game, when head coach Kyle Shanahan was asked if the starters would see action, he stated, “Not all of them, but I expect a number of starters to play, unlike last week."

Brock Purdy and backup Mac Jones did not see any action in the last game and will likely see some in this game. The 49ers are high on rookie WR De'Zhaun Stribling, and he and Purdy have clicked, big time, in camp. It remains to be seen if they will hook up Thursday night, but San Fran may have hit gold with Stribling.

Adrian Martinez and Kurtis Rourke are battling out for the #3 QB spot, and both played in Week 1. However, Rourke is injured and will not play against the Chargers.

The 49ers saw a lot of Martinez and Rourke in the last game, as the team passed for 238 yards, but no backup running backs helped their cause, with the team rushing for only 84 yards, averaging three yards per carry.

The key players, Christian McCaffrey, Dre Greenlaw, Trent Williams, and Fred Warner, will likely not see the field in this game. They are vets with injury histories and Shanahan will be cautious with them.

Chargers Will Play Starters Less 

The Chargers had a joint practice with the 49ers on Tuesday, and beforehand, Chargers head coach John Harbaugh told the press that his starters would play in one series in the Thursday night game. So do not expect Justin Herbert or the starters to see much of the field.

L.A. may have an advantage in this game, as their new offensive coordinator, Mike McDaniel, is the former OC of the 49ers.

In the Chargers' win over the Texans in the first preseason game, Trey Lance solidified his backup QB role, passing for 164 yards, and the L.A. defense came up big, holding the Texans to only 209 total yards.

The Chargers rushed for over 100 yards in the win over the Texans but were not impressive in the run game, where Lance was tied for the team lead with 27 rushing yards. The team will lean on the run in this game, looking to see who will pair with the top backs Omarion Hampton and newcomer Keaton Mitchell.

49ers vs. Chargers Predictions 

49ers to cover the spread (-1.5, DraftKings) 

Not surprisingly, in the second preseason game, neither starter will see much action, but the 49ers may play theirs more, with Harbaugh saying his starters will see only one series. Purdy and the established Mac Jones will likely see most of the time under center for San Fran, and with their pass game and solid defensive backups, look for the 49ers to win and cover.

Under 38.5 

Both teams went under in their first preseason games, and I'm looking for that to happen again. Sure, Purdy and Jones may air it out some, but each team will be looking at running backs, so the run game will be prevalent. With the ground game a focal issue for both teams, it will lead to a lower-scoring affair, so the Under is the pick.

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