4:25 p.m. ET | CBS
Matchup rating: 72.9 | Spread: NE -1.5 (44)
What to watch for: The Patriots have turned the ball over seven times in their past two games, both losses. The 49ers have created just six takeaways all season. If the Patriots continue to be sloppy with the football, they could be looking at back-to-back regular-season home losses for the first time since the 2008 season. -- Mike Reiss
Bold prediction: New England quarterback Cam Newton will rush for 90-plus yards. Believe it or not, Newton has only four such games in his career and hasn't hit the 90-yard mark since 2017. But the 49ers have struggled to contain mobile quarterbacks, allowing 231 rushing yards to QBs so far this season, most in the NFL. -- Nick Wagoner
Stat to know: 49ers quarterback Jimmy Garoppolo is averaging 7.4 yards per attempt this season (18th in the NFL), down from 8.4 in 2019 (third).
Betting nugget: New England is 41-16 ATS following a loss since the start of the 2003 season and is 52-27 ATS after a loss under coach Bill Belichick. Read more.
Wagoner's pick: Patriots 24, 49ers 20
Reiss' pick: Patriots 23, 49ers 20
FPI prediction: NE, 50.3% (by an average of 0.2 points)
Matchup must-reads: Garoppolo has questions to answer three years after trade ... Analytics supported Belichick going for 2 in Patriots' defeat ... Belichick effusive in praise for "great" TE Kittle ... Patriots QB Newton says "no need to press the panic button" after loss to Broncos