NFL Week 6 gets underway on Thursday Night Football with our staff’s Seahawks vs. 49ers picks tonight. The game will kick off at 8:15 p.m. ET and will be broadcast exclusively on Prime Video.
Both teams suffered major upset losses at home last week. The Seahawks (3-2) lost 29-20 to the Giants as 6.5-point favorites, while the 49ers (2-3) blew a double-digit lead in the fourth quarter and lost 24-23 to the Cardinals.
The NFC West is up for grabs entering this game. The Seahawks have a one-game lead over the Cardinals and 49ers, and this is their first divisional game of the season. Even the Rams aren’t totally out of the race despite being 1-4.
As of Wednesday at 4 p.m. ET, 63% of the bets and 75% of the money was on the 49ers. The over was also getting 76% of the bets and 67% of the money. We have an expert backing both of those NFL predictions, as well as a player prop.
49ers vs. Seahawks Picks, Predictions
| Game | Time (ET) | Pick |
|---|---|---|
  | 8:15 p.m. | |
| 8:15 p.m. | |
| 8:15 p.m. | |
Always shop for the best price using our NFL Odds page, which automatically surfaces the best lines for every game. | ||
John LanFranca's 49ers vs. Prediction
The Seahawks defense has been exposed the last couple of weeks and with only a few days to prepare for a Kyle Shanahan-led attack, I have my doubts they can right the ship.
Last week, the Giants had no problem sustaining drives against Seattle and probably should have led the game wire to wire had it not been for a fumble on the goal line in the first quarter. Rookie Tyrone Tracy started his first NFL game and became the first player to have 15 carries in a game this season and have all of them go for positive gains. The Seahawks front seven cannot create havoc for the opposing offense.
To make matters even more difficult, star cornerback Tariq Woolen will miss this game. He'll be replaced by rookie Nehemiah Pritchett, who has played a grand total of 20 defensive snaps this season. This is just another factor leading me to believe the 49ers offense should be able to successfully attack all levels of the field.
The Niners passing attack has been the second-most explosive in the NFL with 11.8% of their attempts going for 20 or more yards. It's also fair to expect positive regression in the red zone for the 49ers. After being the best in the league in the red area in 2023, they have fallen to 30th in the rate at which they are converting these opportunities into touchdowns. This seems more like an outlier to begin this season.
I am expecting an efficient offensive performance from the 49ers against a reeling Seahawks defense. I like the road team to take care of business on Thursday night.
Pick: 49ers -3.5 (-110)
Billy Ward's Over/Under Bet
By Billy Ward
After opening at 46.5, the total in 49ers-Seahawks has been bet up throughout the week. As of Wednesday afternoon, FanDuel was the only sportsbook with 48.5. Everywhere else was up to 49 and ESPN BET was even up to 49.5.
A total moving two to 2.5 points is a fairly strong signal for how the market views this game. My initial read was that it had gone too far — until I checked the injury report.
Both teams are fairly healthy on offense — the only starter for either team to carry an injury tag is George Kittle, although Christian McCaffrey is also out for the 49ers. Kittle will almost certainly play since he’s played through the injury in each of the past two weeks.
It’s a different story on the defensive side of the ball. The 49ers had three defensive starters miss Tuesday’s practice, with one already ruled out. The Seahawks have three starters listed as questionable, including two members of their defensive backfield. Plus, San Francisco will be without kicker Jake Moody, which should hopefully lead to the Niners going for it on fourth down more often than usual in Seattle territory.
I’d take over 49 if I had to, but try to bet the over at 48.5 if possible.
Pick: Over 48.5 (-112)
Grant Neiffer's 49ers vs. Seahawks Best Bet on DK Metcalf
DK Metcalf may only have two touchdowns this season, but he's still the clear alpha in this offense. He's averaging close to 100 receiving yards over the last Seahawks' last four games.
Seattle hasn't faced an especially tough schedule this season and has struggled heavily in the red zone. The Seahawks have completed just four of the 12 passes they've attempted inside the 20-yard line this season, but I don't expect that to continue.
Metcalf was fantastic in the red zone last season with six touchdowns from a massive 26 targets, which ranked sixth in the league. The game total is sitting at 49 and the spread is 49ers -3.5, which indicates this should be a pretty close game. With that, I think Metcalf is much more likely to find the end zone than his odds imply.
Pick: DK Metcalf Anytime TD Scorer (+150)
