Seahawks vs. 49ers prediction: Can San Francisco overcome injuries, short week at No. 1 seed Seattle?

The Seattle Seahawks clinched the NFC West division title and the conference's No. 1 seed with a 13-3 victory over the San Francisco 49ers in Week 18.  The three points San Francisco scored that night are tied for their fewest in a game under head coach Kyle Shanahan (since 2017). 

When the Seahawks return to action in the NFC divisional round Saturday night, it will be against those same 49ers. Well, not exactly the same San Francisco bunch with All-Pro tight end George Kittle suffering a season-ending torn Achilles tendon in the 49ers' 23-19 wild card round win at the defending Super Bowl champion Philadelphia Eagles.

Following that victory on Sunday and entering the divisional round rematch in Seattle on Saturday night, the 49ers will have flown 3,000 miles and will be coming off a short week. Meanwhile, the Seahawks will be fresh from 13 days of rest. Teams in San Francisco's predicament, playing in the playoffs on a short week against a team coming off a bye, are just 5-10 in that scenario since divisional realignment in 2002. However, the No. 6 seed Washington Commanders did upset the top-seeded Detroit Lions in this exact situation last season. 

Can the 2025 NFC No. 6 49ers follow in the Commanders' footsteps? Or will the Seahawks lock down Brock Purdy and Co. for the second game in a row? Let's dig into that and more in our preview and prediction below. 

Where to watch Seahawks vs. 49ers live

• Date: Saturday, Jan. 17 | Time: 8 p.m. ET
• Location: Lumen Field (Seattle, Washington)
• TV: FOX | Stream: Fubo (try for free)
• Follow: CBS Sports App
• Odds: Seahawks -7, O/U 45.5 (via DraftKings Sportsbook)

49ers vs. Seahawks: Need to know

Can the 49ers overcome a seemingly never-ending list of injuries? 

It's divine intervention that the 49ers are still alive in the divisional round of the playoffs. San Francisco has the most player games missed because of injuries among playoff teams this season, including the playoffs, at 287. Naturally, they also have the most games missed by Week 1 starters (their key players) among playoff teams this season. 

All-Pro edge rusher Nick Bosa, All-Pro linebacker Fred Warner and now All-Pro tight end George Kittle all won't be available to San Francisco in the divisional round at the No. 1 seed Seattle Seahawks while playing on a short week on Saturday night. Head coach Kyle Shanahan is one of the NFL's most innovative coaches there is, but there comes a point when the missing talent on the field supersedes high-level X's and O's. 

When the 49ers came into Lumen Field and escaped with a 17-13 victory in Week 1, San Francisco did so after Bosa strip-sacked Seahawks quarterback Sam Darnold to seal the victory. They'll have to figure out how to spook Darnold in Seattle this time around without the 2022 NFL Defensive Player of the Year. 

Will Sam Darnold be able to avoid committing the big mistake? 

As mentioned above, Darnold getting strip-sacked was the final nail in the coffin of the Seahawks' 17-13 Week 1 home loss to the 49ers. That's worth noting as well as the reality that his level of play is trending the wrong direction entering the postseason with 8 total touchdowns to 10 turnovers since Week 11. His NFL-most 20 turnovers (14 interceptions and 6 fumbles lost) in 2025 reveal a player still prone to making a crucial mistake at any time. 

A year ago, Darnold melted down after helping power the Minnesota Vikings to a 14-win regular season. He absorbed an NFL playoff record nine sacks in his postseason debut last year. That's a massive reason why the Vikings lost 27-9 in the wild card round to the Los Angeles Rams and decided to let him leave in free agency this past offseason. 

He played a clean game in the Week 18 win against the 49ers, completing 20 of his 26 passes for 198 yards. That effort was aided by the Seahawks taking the ball out of his hands and handing the ball off 39 times, the second-most rushing attempts for Seattle in a game this season. The only game they ran the ball more was in a 44-22 Week 10 win over the Arizona Cardinals in which they ran the ball a whopping 46 times. Expect to see a lot of Kenneth Walker III and Zach Charbonnet on Saturday night. 

Can Brock Purdy put on his Superman cape and power the 49ers past the Seahawks' No. 1 scoring defense? 

San Francisco 49ers quarterback Brock Purdy has been playing like a top-five quarterback since returning from his turf toe injury in Week 11. As a result, the 49ers have won seven of their last eight games in that stretch. The one loss was of course against the Seahawks in Seattle's last game played in Week 18. 

A big reason for Purdy's struggles (127 yards and an interception on 19 of 27 passing) in Week 18 was the absence of All-Pro left tackle Trent Williams (hamstring). Williams' not suiting up contributed to Purdy being pressured on 46.9% of his dropbacks that night, the third-highest pressure rate he has faced in a game this season. Even with Williams back, will Purdy be able to play his best against the best? The Seahawks are the NFL's No. 1 scoring defense (17.2 points per game allowed), and Purdy has never been able to help lead the 49ers to victory over a top three scoring defense in five opportunities since becoming San Francisco's full-time starting quarterback in 2023. 

* Dates back to 2023

49ers vs. Seahawks prediction, pick

Unless Shanahan has more trick play magic in his playbook this week, it's going to be a long night on both sides of the ball for his 49ers. San Francisco is simply too plagued by injuries to power past the No. 1 seed Seahawks on the road on a short week. Their divisional round matchup will look a lot like Seattle's 13-3 victory in Week 18. 

Pick: Seahawks 24, 49ers 16 | Seahawks -7, Under 44.5