Week 6 in the NFL kicks off from Lumen Field as the Seattle Seahawks are set to host the San Francisco 49ers in an NFC West matchup on Thursday night. 

This is the first time these two division rivals will square off this season after the Niners swept the season series in 2023. This time around, the Seahawks find themselves sitting atop the NFC West at 3-2 but are looking to snap a two-game losing skid that they are currently riding coming into Week 6. As for San Francisco, they enter this matchup 2-3 of the year and are trying to rebound after allowing the Arizona Cardinals to rally from a 23-10 halftime deficit and beat them at home on Sunday. 

The winner of this matchup will, for the moment, be in first place in the NFC West, so there is plenty on the line. Before we reach kickoff, let’s dive a bit deeper into these two rivals. 

49ers vs. Seahawks where to watch

Date: Thursday, Oct. 10 | Time: 8:15 p.m. ET
Location: Lumen Field (Seattle)
Stream: Prime Video
Follow: CBS Sports App   
Odds: 49ers -3.5; O/U 49.5 (via SportsLine consensus)

When the 49ers have the ball

It’s worth pointing out that Mike Macdonald will be lurking on the sidelines as Seattle’s head coach, and he did a fantastic job at disrupting Brock Purdy when he was the Baltimore Ravens defensive coordinator last year. In that matchup, Purdy threw a career-high four interceptions and finished with a passer rating of just 42.6 against Macdonald’s defense, so while this is an entirely different roster than he faced a year ago, the 49ers quarterback will be looking to avoid a similar result against the same guy pulling the strings defensively. 

So far this season, Purdy has been stellar, but injuries around the skill position players have contributed to this offense not reaching the heights we saw a season ago. Part of that, of course, is the absence of running back Christian McCaffrey, as the reigning NFL Offensive Player of the Year is sidelined with an Achilles injury. Where San Francisco misses him the most is in the red zone. The team ranks 30th in red zone touchdown percentage this season (41%) after being first in this category (67%) in 2023. McCaffrey had 18 total red zone touchdowns last season. So, for this unit to turn the tide, it’ll need to be far more efficient when it gets into the red area with the likes of running back Jordan Mason, wideouts Deebo Samuel and Brandon Aiyuk, and tight end George Kittle. 

It’s also notable that the 49ers will have a new kicker for this game, with Jake Moody sidelined due to a high ankle sprain. Earlier this week, the club signed veteran kicker Matthew Wright. 

When the Seahawks have the ball

All eyes will be on Seattle’s “big three” at wide receiver in this game. DK Metcalf, Jaxon Smith-Njigba and Tyler Lockett have formed quite the three-headed monster in the Seahawks passing attack. 

Entering Week 6, the offense averages 6.5 yards per play when they are all on the field at the same time, which would rank Seattle’s offense second in the entire NFL. Meanwhile, the offense averages 4.9 yards per play when they aren’t on the field together. That would tie the offense with the likes of the Carolina Panthers and Los Angeles Chargers in the bottom half of the league. The Seattle offense seems to know how impactful this trio is, as it has increased the workload together on the field this season (58% of plays) compared to 2023 (48%). 

As it relates to their quarterback, Geno Smith, he’ll need to buck what has proved to be a rather disastrous trend against these 49ers. In his last three seasons, Smith is 0-4 against San Francisco with three touchdowns and three interceptions.  

49ers vs. Seahawks key matchup

One of the more curious aspects of Seattle’s loss to the New York Giants on Sunday was its abandonment of the running game. While Geno Smith dropped back and threw it 40 times, the Seahawks ran the ball just 11 times. Against this opponent, they should look to lean a little bit more on the ground attack since they should be able to attack the San Francisco run defense in a similar way Arizona did in its upset in Week 5. This season, the Niners are giving up 110.8 rushing yards per game. That ranks as the ninth-fewest in the league. Pretty good, right? Well, when you look at their opponents’ yards per rush attempt average, that ranks tied for the sixth-highest in the league (4.7).  

This could be an opportunity for Kenneth Walker III, Zach Charbonnet, and even Smith to do damage against this sneaky lackluster run defense of the 49ers. 

49ers vs. Seahawks prediction

History says to back the 49ers in this spot, as they’ve had the Seahawks number in their recent matchup. San Francisco has won five straight games against its division rival and has covered in all but one of those contests. That lone against-the-spread loss was because it failed to cover a 14.5-point spread (won by 12). Kyle Shanahan also seems to get his team ready to go in these divisional games under the prime-time setting, as it is 7-0 straight-up and against the spread against NFC West foes in its past seven prime-time games. Seattle also has struggled with quick turnarounds, owning a 0-4 record in its past four Thursday games. 

Projected score: 49ers 27, Seahawks 23
The pick: 49ers -3.5