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Las Vegas Raiders vs. San Francisco 49ers prediction, pick for NFL Preseason on 8/16/25

Las Vegas Raiders vs. San Francisco 49ers prediction, pick for NFL Preseason on 8/16/25

Published:

By: Charlie Cummings

NFL Preseason Week 2 is here. And while the stakes aren’t the same, or the rivalry itself, games between the San Francisco 49ers and Las Vegas Raiders always bring intrigue.

The Raiders are -4.5 favorites at home in this game on DraftKings Sportsbook. Las Vegas is a -198 favorite on the Moneyline with the total set at 40.5 points. Let’s get into a preview, prediction, and pick for this 49ers-Raiders game.


Raiders vs. 49ers preview, prediction

San Francisco 49ers

Hello reader. Do you have two legs and two hands? Can you run in a straight line, or perhaps diagonally? Congratulations, the 49ers are going to try you out at wide receiver.

Brandon Aiyuk will miss the early part of the season. Starting slot receiver Jauan Jennings is hurt and seeking a new deal. Rookie Jordan Watkins is out for the preseason. Longtime depth option Trent Taylor is on IR, as is new signee Equanimeous St. Brown. So, step on up if you want to play outside receiver for the 49ers.

The rest of the offense is largely settled. There’s a critical backup RB competition with Christian McCaffrey’s injury history lingering, but Isaac Guerendo and Jordan James are both hurt. Patrick Taylor is a capable depth option and Jeff Wilson is back. Other than the backfield and the receiving core disaster, their offense is set and only need minor tune-ups in the preseason.

San Francisco’s defense is — you guessed it — riddled with injuries. Projected starting DT Kevin Givens is out for the foreseeable future with a pec injury. First-round pick Mykel Williams, slated to be Nick Bosa’s opposite, missed the first exhibition game with a knee injury. They hammered the defensive line hard in the draft and have lots of depth, but it’s a point of concern with the regular season fast approaching.

Luckily for their staff, the back seven needs less work. Their linebackers are set, and the outside corners are locked in. There’s potential for a battle at slot corner and free safety, but they have a depth of options. GM John Lynch drafts so well, and despite losing several free agents, only two potential starting spots will likely be filled by new signings. That’s an impressive feather in his cap.

Las Vegas Raiders

Las Vegas has a strikingly similar profile of battles to settle on offense. The offensive line is solidified, they have a no-doubt starting QB in Geno Smith, and Ashton Jeanty will get all the touches he can handle. There’s a healthy competition at backup running back and depth offensive line spots, but the real drama is at wide receiver.

Jakobi Meyers and Tre Tucker have their starting spots locked in. Beyond that, who knows? Vegas has a trio of rookies — Jack Bech, Dont’e Thornton Jr., and Tommy Mellott — all vying for snaps. They’ve got holdovers and veteran signees in Alex Bachman, Phillip Dorsett, Marquez Callaway, and others. It’s bound to be a heated competition down the stretch.

You would hardly recognize this year’s defense compared to last year’s. Their starting defensive line should comprise of holdovers from last year, but the back seven is nearly brand new. All three projected starting linebackers are new signees: Germaine Pratt, Elandon Roberts, and Devin White. They also have Jamal Adams (yes, that Jamal Adams) and Jaylon Smith signed as backup options.

And that’s not where the newness ends. Both projected starting outside corners, Eric Stokes and Darien Porter, are new arrivals. The former comes in via free agency, the latter via the draft. Jeremy Chinn was signed as well to bolster the back end. That makes six of 11 newbies projected starters. New GM John Spytek wasted no time upgrading this defense. While there aren’t many battles to be settled, there will be an onus on the staff to play the starters more snaps than usual to build cohesion.

49ers vs. Raiders pick, best bet

There’s a good reason why the Raiders are favored in this one. First and foremost, with the starting QBs projected to play little (if at all), the backups are in the spotlight. Mac Jones vs. Aidan O’Connell tips the scales in favor of the Raiders. But it’s not the quarterback room alone; Las Vegas has advantages up and down the lineup due to San Francisco’s health concerns.

A lot of starters for the Niners won’t even suit up due to existing injuries or fear of further injuries. With a lot of depth options injured as well, things are getting thin at crucial positions. And with the Raiders healthy and motivated to play a lot of the starters, this matchup is very much in their favor.

Best Bet: Las Vegas Raiders -4.5 (-105)

Charlie Cummings is a Bay Area-born writer living in Denver. A basketball junkie, he specializes in NBA and WNBA content, but also dabbles in soccer, baseball, football and hockey. You can find him on Twitter @klaytheist11 where he’s posting through it on a daily basis.
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I am a promoter at DraftKings and am also an avid fan and user and may sometimes play on my personal account in the games that I offer advice on. Although I have expressed my personal view on the games and strategies above, they do not necessarily reflect the view(s) of DraftKings and do not constitute a representation that any particular strategy will guarantee success. All customers should use their own skills and judgment in building lineups. I may also deploy different players and strategies than what I recommend above. I am not an employee of DraftKings and do not have access to any non-public information.