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Jimmy Garoppolo of the San Francisco 49ers throws a pass against the Arizona Cardinals at Estadio Azteca on Nov. 21, 2022 in Mexico City, Mexico.
Jimmy Garoppolo of the San Francisco 49ers throws a pass against the Arizona Cardinals at Estadio Azteca on Nov. 21, 2022 in Mexico City, Mexico. Photo by Sean M. Haffey/Getty Images via AFP.

The 6-4 San Francisco 49ers have won three straight and welcome the 4-7 New Orleans Saints. Can the Saints upset the heavily favored Niners? Read on for our best Saints-49ers picks. 

The 49ers are feeling good, coming off a third straight win to improve to 6-4. After a slow start, they’re now in the NFC West driver’s seat and appear to be one of the league’s most dangerous teams.

The Saints continue to look awful, but they did just pick up their fourth season win in 10 games. That was over the Los Angeles Rams, though, and we already know the adversity that franchise has faced.

Here are our Saints-49ers Week 12 NFL picks (odds via PointsBet, FanDuel Sportsbook and DraftKings Sportsbook; pick confidence based on a 1-to-5-star scale).

Saints vs. 49ers Game Info

  • Date: Sunday, Nov. 27, 4:25 p.m. ET
  • TV: FOX
  • Location: Levi’s Stadium, Santa Clara, CA
  • Weather: 62 degrees, 0% of precipitation, 8-mph NW winds

Saints vs. 49ers Odds

Saints vs. 49ers Odds Analysis

The 49ers are favorites among books and drew an opening line of -9. The line remains there and the Niners are getting 78% of both the cash and tickets.

The Over/Under has gone up two points from the opening number of 41.5. The Over is favored in both cash (75%) and tickets (74%).

Saints vs. 49ers Picks

  • Spread: 49ers -8.5 (-110 via FanDuel) ★★★★
  • Over/Under: Under 43 (-110 via DraftKings) ★★★★★      
  • Prop: Alvin Kamara under 50.5 rush yards (-115 via PointsBet) ★★★★★      

Saints vs. 49ers ATS Pick

49ers -8.5 (-110)★★★★

While it’s scary that 49ers wide receiver Deebo Samuel is questionable, it’s about the only thing keeping me from laying the points with the home team.

San Francisco is now 2-1 against the spread as the favorite, pretty good when you consider it's covered just five times in 10 games. The biggest thing, though, is the defense.

The Niners are top 10 in rushing and passing DVOA, grading out as the NFL's seventh-best unit. By contrast, the Saints continue look incompetent on offense, mustering up just 50 combined points in their last three matchups and getting some very fleeting numbers from quarterback Andy Dalton.

The Saints rank 23rd in offensive DVOA and even in victory last week ran the ball for just 88 yards. Sure, Dalton looked incredible against a broken down L.A. Rams secondary, but this should be a much different story. Without points, New Orleans won’t cover.

Saints vs. 49ers O/U Pick

Under 43 (-110)★★★★★   

The Under cashed in three of the past four games the Saints played, because the Saints simply can’t score points. Now, they face a top-10 defense which can totally shut down their rushing attack and torment Dalton, who's simply not a good quarterback. With the Niners focused on the run for most of the second half, there’s no way this game goes Over the total.

The Niners should have total control of the game and it should go incredibly slowly. San Francisco is 28th in total pace, going 29.83 seconds between plays on average, and when leading by a touchdown or more that number increases to 31.12. In the second half? 30.41. In any scenario, it's a bottom-three team in pace. This game is not going Over.

Saints vs. 49ers Prop Pick

Kamara under 50.5 rush yards (-115) ★★★★★ 

There’s no reason for the Saints to run at all in this matchup, as they’ll be losing for most of the game. New Orleans only runs the ball 41.31% of the time, an NFL 16th, and that's just 25 carries per game.

New Orleans running back Alvin Kamara eclipsed 50 yards only four times this season and is about to run into the league's ninth-best rushing defense. It’s not going to end well, and if the Saints were smart they’d try to hit a few home runs early in this game.

Where to Bet on Saints vs. 49ers  Picks

Here are our top-rated sportsbooks:

Saints-49ers picks made 11/25/2022 at 8:59 p.m. ET