Chargers vs 49ers Odds, Pick, Prediction: NFL Preseason Preview

Editor's note: This story was written before the 49ers reportedly traded Trey Lance to the Cowboys. 

There’s a San Francisco soap opera brewing as we head into its preseason finale, and it can’t be ignored as we make our 49ers vs. Chargers pick.

The saga surrounding Trey Lance, the third overall pick in the 2021 NFL Draft, took center stage this week. The 49ers, of course, traded a king’s ransom to move up and select Lance, who has failed to meet the hype, recently losing the QB2 battle to Sam Darnold and being relegated to the third string.

Lance didn’t exactly take the news in stride, skipping out on Wednesday’s practice with the team’s blessing. San Francisco alluded that all options are on the table with the young quarterback, including fielding trade offers from other teams.

Meanwhile, head coach Kyle Shanahan announced the 49ers will play their starters in the final exhibition match at Levi's Stadium, while the Chargers will rest theirs. Add it all up in the Chargers vs. 49ers odds and I’m favoring a pick on San Francisco to cover as heavy favorites on Friday night.

Both teams are legit Super Bowl contenders, but the 49ers are most likely the only team that’ll look like an elite squad on Friday. After all, the Brock Purdy-Sam Darnold QB combo that’ll kick off the first half is head and shoulders above the Bolts' tandem of Easton Stick and Max Duggan.

This marks the second tune-up game for Purdy in his return from offseason elbow surgery. He looked like his usual self in his brief stint a week ago, completing 4-of-5 passes for 65 yards and a 118.8 QB rating.

However, it’s more than just the quarterbacks that give the 49ers a significant edge.

We’re expected to see Christian McCaffrey, Deebo Samuel, Brandon Aiyuk and most of San Francisco's explosive offensive weapons, while Stick and Duggan likely square off against Arik Armstead, Fred Warner, Tashaun Gipson and the rest of the 49ers’ lights-out defense. Hardly a fair fight, don’t you think?

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At the same time, all eyes will be on Trey Lance whenever he enters the game. The most likely scenario is he remains a 49er. However, they're not ruling out a trade, so he'll certainly be showcasing his talents for the other 31 NFL teams.

Even though he lost the backup QB competition, Lance has impressed over his first two preseason games. Despite completing just 15-of-31 attempts, he's thrown for 194 yards while rushing for 67 yards on 16 carries.

I suspect San Francisco races out to a quick lead, and then Lance and company extend it in the second half.

Those who’ve followed me this preseason should be familiar with my first half “back the starters, fade the backups" modus operandi.

But in this case, mostly because of Lance, I'm taking the 49ers laying 7.5 points over the full 60 minutes. The public agrees, with 56% of the bets and 66% of the money backing them to cover.

It’s a fluid situation, though. Should Lance somehow wind up skipping the game, you may want to consider pivoting to a first half San Francisco cover. However, if he does suit up as expected, I’m sticking with the 49ers laying the points for the entire game.