49ers vs. Seahawks Prediction, NFL Week 5 Odds & Best Bets (10/11)

Fact checked at 7:18 AM ET, Oct 11, 2026

Odds as of Oct 11, 7:15 AM ET

San Francisco is 4-0, scoring 30.5 points a game (second in the league), and Brock Purdy has 11 touchdown passes, one interception and zero sacks taken. Now the 49ers go to Lumen Field to play the defending champion Seahawks (3-1), who have seen this offense twice since New Year's and allowed nine points total. Seattle won those January games 13-3 and 41-6, and San Francisco never reached the end zone.

We think Seattle's defense slows the 49ers again. It allows 18.3 points a game, fifth in the league, and 161.2 passing yards, second behind the Rams. San Francisco has done most of its damage against softer defenses than this one, and it shows up without fullback Kyle Juszczyk, who is out with a knee injury. Both of our picks are 49ers Unders, and both need that kind of game.

Friday's final injury report rules out four 49ers: Juszczyk, defensive end Nick Bosa, defensive tackle James Thompson Jr. and safety Marques Sigle. Cornerback Upton Stout is questionable. So is defensive end Mykel Williams, though the team activated him Saturday and he is set for his season debut. Seattle will be without running back Zach Charbonnet, linebacker Chazz Surratt and cornerback Julian Neal, and running back George Holani is questionable. Neither quarterback is on the report, so it is Purdy against Sam Darnold. Christian McCaffrey practiced in full Thursday and Friday and carries no designation. Neither does Mike Evans, who is playing through a rib injury.

Seattle is a 3-point favorite at -115. The total is 45.5, down a point from 46.5. Seattle gets a sunny afternoon in the upper 50s with a light north wind, so weather is not a factor. Kickoff is at 4:25 PM ET on FOX.

49ers vs. Seahawks Predictions

• Pick #1: Brock Purdy Under 228.5 Passing Yards (-112)
• Pick #2: Christian McCaffrey Under 50.5 Rushing Yards (-114)

PICK #1: Brock Purdy Under 228.5 Passing Yards (-112)

Four quarterbacks have faced Seattle this season and none has thrown for 190 yards. Drake Maye had 178, Jacoby Brissett 95, Marcus Mariota 183 and Justin Herbert 189. Add it up and Seattle has given up 645 yards on 124 attempts, or 5.2 per throw.

Purdy has gone over this number twice in four games (205, 287, 297, 218), but look at who he did it against. The 287 and 297 came against Miami and Arizona, which rank 20th and 23rd in passing yards allowed. He had 218 against Denver, which is 22nd. The one good pass defense on his schedule was the Rams, who rank first, and he needed 34 attempts to get to 205.

Volume is the other problem for the Over. San Francisco has thrown 34, 22, 27 and 30 times, about 28 a game, and at that rate Purdy needs roughly eight yards per attempt to clear 228.5. He got 127 yards on 27 attempts in the 13-3 loss and 140 on 27 in the 41-6 playoff loss. Seattle already has 11 sacks and six interceptions this season.

The -112 price implies a 52.8% chance. What beats it is a game where San Francisco falls behind and Purdy throws 40 times. He put up 277 yards on 35 attempts at Lumen Field in last season's opener. He also has more to work with than he did in January: Evans and Deebo Samuel weren't 49ers then, and Seattle's secondary has since lost Riq Woolen and Coby Bryant.

PICK #2: Christian McCaffrey Under 50.5 Rushing Yards (-114)

McCaffrey's own numbers say Over. He has run for 68, 23, 75 and 52 yards, topping 50.5 in three of four games, and he is averaging 4.4 yards a carry. So this is a bet on the opponent and on the missing fullback, at a price (-114) that implies 53.3%.

No running back has gained more than 51 yards against Seattle this season. The lead backs it has faced finished with 51, 29, 36 and 45, and running backs as a group have 305 yards on 91 carries, 3.4 a carry. McCaffrey's carry counts are 10, 10, 15 and 15. At Seattle's rate he would need 16 to get over the number, and Kaelon Black has taken between four and 14 carries in every game.

This defense has also had his number. In three games against Seattle last season McCaffrey ran for 69 yards on 22 carries, 23 on eight and 35 on 11. That is 3.1 a carry.

Then there is Juszczyk. He has played between 41% and 56% of the offensive snaps in every game, and no team in the league has used two-back sets more than San Francisco. Seattle coach Mike Macdonald said he expects the 49ers to go with multiple tight ends instead, and San Francisco elevated tight end Jack Stoll from the practice squad on Saturday.

Seattle's run defense is not airtight. The Chargers ran for 147 yards on it last week, 40 of them by Herbert. And McCaffrey's way over is a second half with San Francisco in front, when his carries climb. That is the opposite of the game that hurts Purdy's Under, so the two bets don't share the same worst case. Both cash in the kind of game Seattle's defense forced twice in January.

21+ (18+ where permitted). Odds subject to change. If you or someone you know has a gambling problem, call 1-800-GAMBLER.