The 49ers (0-0) and the Seahawks (0-0) square off Sunday in Seattle in a Week 1 NFC West matchup.
The big news re: this game is without question the availability of Christian McCaffrey (calf). If the All Pro is unavailable, the Niners’ offense already beset by injuries to other offensive pieces will be far less dynamic and dangerous. The San Francisco defense is healthy but will need help from the offense if the 49ers are to leave Lumen Field victorious.
The Seahawks enter the season with a new quarterback, Sam Darnold, and a new wideout to pair with Jaxon Smith-Njigba in Cooper Kupp. The defense remains one of the fastest in the league but will be tested should Riq Woolen (illness) not dress.
Lets take a deeper dive into this week’s matchup between the 49ers and the Seahawks.
NBC Sports has all the latest info and analysis you need, including how to tune in for kickoff, odds from DraftKings, player news and updates, and of course our predictions and best bets for the game from our staff of experts.
Game Details and How to watch the 49ers vs. Seahawks live Sunday
- Date: Sunday, September 7, 2025
- Time: 4:05PM EST
- Site: Lumen Field
- City: Seattle, WA
- Network/Streaming: FOX
Want to check out the other games on the NFL schedule this week? We’ve got you covered right here on NBC Sports with all the matchup, venue, game-time and TV/streaming info so you won’t miss any of the action!
Game odds for the 49ers vs. the Seahawks
The latest odds as of Friday courtesy of DraftKings:
- Moneyline: San Francisco 49ers (-122), Seattle Seahawks (+102)
- Spread: 49ers -1.5
- Total: 43.5 points
This game opened at 49ers -1.5 with the Total set at -45.5.
Be sure to check out DraftKings for all the latest game odds & player props for every matchup this week on the NFL schedule!
Quarterback Matchup for San Francisco vs. Seattle
- 49ers Expected Starting QB: Brock Purdy
Last Season: 15GP, 300-455 (65.9%), 3,864 yards, 20 TDs, 12 INTs, Sacked 31 Times - Seahawks Expected Starting QB: Sam Darnold
Last Season (with Minnesota): 17GP, 361-545 (66.2%), 4,319 yards, 35 TDs, 12 INTs, Sacked 48 times
49ers vs. Seahawks team stats, betting trends
- The 49ers are on a 3-game win streak in Seattle
- The 49ers have failed to cover the Spread in their last 3 games against NFC West teams
- 5 of the 49ers’ last 7 road trips to Seattle have gone over the Total
- In 12 GP last season with the Rams, Cooper Kupp was targeted 100 times and caught 67 passes for 710 yards
49ers Player Injuries
- RB Christian McCaffrey (calf) is questionable for Sunday’s game
- WR Jauan Jennings (calf) is questionable for Sunday’s game
- WR Jordan Watkins (ankle) is questionable for Sunday’s game
- RG Dominic Puni (knee) is questionable for Sunday’s game
- DE Yetur Gross-Matos (knee) is questionable for Sunday’s game
Seahawks Player Injuries
- RG Anthony Bradford (back) is questionable for Sunday’s game
- CB Riq Woolen (illness) is questionable for Sunday’s game
- NT Johnathan Hankins (back) has been declared out of Sunday’s game
- WR Jake Bobo (concussion) is questionable for Sunday’s game
- WR Dareke Young (hamstring) is questionable for Sunday’s game
- WR Cody White (shoulder) is questionable for Sunday’s game
Rotoworld Bet Best Bets
Please bet responsibly. If you or someone you know has a gambling problem, call the National Gambling Helpline at 1-800-522-4700.
Drew Dinsick (@whale_capper): Seattle Seahawks ML
Niners start the season in division on the road against a Top 10 defense having had a preseason littered with important players missing time due to injury, particularly in the WR room. Purdy and Shanahan have not proven they have the answers to the Mike McDonald defensive scheme which will make things tough if the Niners investment to fix the run defense hasn’t paid dividends yet. Ultimately, I expect SF to warrant a Top 10 rating, but it may take weeks for injuries to abate and player development to progress in order to reach this potential.
Jay Croucher (@croucherJD): Seattle Seahawks +2.5
I got this number prior to the news about McCaffrey. Brock Purdy has had some loud struggles against Mike Macdonald’s defense, which closed the season as an elite unit and should bring that form into week 1 against a Niners pass catching corps that isn’t as pristine as it will be two months from now. San Francisco’s defense has been terrible against the run for two years now, which Clint Kubiak’s scheme and Seattle’s improving OL should exploit.
Our model calculates projections around each moneyline, spread and over/under bet for every game on the NFL calendar based on data points like past performance, player matchups, stadium information and weather forecasts.
Once the model is finished running, we put its projection next to the latest betting lines for the game to arrive at a relative confidence level for each wager.
Best bets our model is projecting for this week’s game between the 49ers and the Seahawks:
- Moneyline: NBC Sports Bet is staying away from a play on the Moneyline.
- Spread: NBC Sports Bet is leaning towards a play ATS on the San Francisco 49ers at -2.5.
- Total: NBC Sports Bet is recommending a play on the over on the Game Total of 43.0.
Rotoworld has you covered with all the latest betting info & tools for NFL with game predictions, player props, futures, and trends!
Follow our experts on socials to keep up with all the latest content from the staff:
● Jay Croucher (@croucherJD)
● Drew Dinsick (@whale_capper)
● Vaughn Dalzell (@VmoneySports)
● Trysta Krick (@Trysta_Krick)
