4:25 p.m. ET | FOX
Matchup rating: 79.5 | Spread: NO -9 (50)
What to watch for: The Saints have emerged as one of the NFL's hottest teams. But they need to avoid a letdown against a 49ers team that has been decimated by injuries. San Francisco's thrilling 48-46 win in the Superdome last year should provide added motivation. -- Mike Triplett
Bold prediction: Saints receiver Michael Thomas will deliver his first big game of the season, going for 110-plus yards and at least one touchdown. In last year's meeting with San Francisco, he posted 11 catches for 134 yards and a touchdown. Opposing offenses have been moving their top receivers around to get them matched up against Niners cornerback Emmanuel Moseley, who is allowing a 109.9 passer rating against when he's the nearest defender. If Moseley is still starting this week, it wouldn't be a surprise if Saints coach Sean Payton does the same with Thomas. -- Nick Wagoner
Stat to know: The 49ers are looking to avoid their first three-game losing streak since Weeks 10-13 of 2018. They have a 22-8 record with Jimmy Garoppolo (IR, ankle) as the starting QB since 2017, but they are just 5-22 with anyone else in that span.
What to know for fantasy: Since Week 5, the 49ers are a bottom-10 defense in opponent completion percentage (67.9%). And Saints QB Drew Brees has completed 78.9% of his passes over his past three games. See Week 10 rankings.
Betting nugget: Since the start of last season, San Francisco is 9-3 ATS on the road, the third-best mark in the NFL over that span, and 6-1 ATS as a road underdog (second-best). Read more.
Wagoner's pick: Saints 37, 49ers 20
Triplett's pick: Saints 30, 49ers 19
FPI prediction: NO, 60.7% (by an average of 3,7 points)
Matchup must-reads: Rice expects 'big things' from 49ers rookie Aiyuk ... NFL sack leaders: Donald, Garrett and Saints' Hendrickson? ... 49ers, Bourne cleared of any COVID-19 protocol violations, source says ... NFC West roundtable: Why the Seahawks, Rams, Cardinals and 49ers would win the NFC East