McCaffrey is still working his way into the game plan, but he has given quarterback Jimmy Garoppolo a safety valve from the pocket. The Saints (4-7) know McCaffrey well and will look to neutralize his activity on Sunday.
The Saints have lost three of their last five games. They will look to get back on track against the 49ers' defense which features star edge-rusher Nick Bosa and linebacker Fred Warner.
Here's a look at the betting details and USA TODAY's NFL staff picks for the Saints vs. 49ers Week 11 game:
Saints at 49ers odds, moneyline and over/under
Spread: 49ers (-8.5)
Moneyline: 49ers (-425); Saints (+350)
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NFL Week 12 odds, predictions and picks
Bills at Lions | Giants at Cowboys | Patriots at Vikings | Broncos at Panthers | Buccaneers at Browns | Ravens at Jaguars | Texans at Dolphins | Bears at Jets | Bengals at Titans | Falcons at Commanders | Chargers at Cardinals | Raiders at Seahawks | Rams at Chiefs | Saints at 49ers | Packers at Eagles | Steelers at Colts
Lorenzo Reyes: 49ers 27, Saints 20
Andy Dalton played well enough to save his job and keep the Saints’ season afloat. This Niners defense, however, is a far tougher test. And with San Francisco at full health and Jimmy Garoppolo minimizing mistakes, it should be a comfortable victory.
Safid Deen: 49ers 31, Saints 17
The 49ers have the first of three straight home games, with a chance to lock up the No. 1 seed in the NFC playoff race this season if they really commit to being the team they looked like when they beat the Cardinals in Mexico. I like San Francisco to beat New Orleans this week.
Lance Pugmire: 49ers 30, Saints 14
As the Dolphins, Buccaneers and seahawks await, San Francisco grasps the urgency and wins convincingly against Andy Dalton and a team that’s 1-3 on the road.
Jarrett Bell: 49ers 31, Saints 20
Nate Davis: 49ers 29, Saints 20
Tyler Dragon: 49ers 26, Saints 1
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This article originally appeared on USA TODAY: New Orleans Saints at San Francisco 49ers: Game predictions, picks, odds