Monday Night Football in Week 12 of the 2025 NFL season is a showdown in the NFC between the Carolina Panthers and the San Francisco 49ers. It could be a crucial game for wild card positioning as Carolina comes in with a 6-5 record and San Francisco is 7-4.
Let’s dive into my Panthers vs. 49ers predictions dive.
Carolina Panthers vs. San Francisco 49ers odds
Moneyline: Panthers +310 / 49ers -395
Spread: Panthers +7.5 (-115) / 49ers -7.5 (-105)
Total: More than 49.5 (-110) / Less than 49.5 (-110)
Carolina Panthers vs. San Francisco 49ers Best Bet No. 1: Over 49.5 (-110)
Brock Purdy is back for San Francisco. The oft-injured quarterback returned in Week 11 and looked as good as ever. He led the 49ers to a 41-22 win over Arizona while completing 19 of 26 attempts for 200 yards with three touchdowns and no interceptions. With the Niners’ offense healthier than it has been all year, more success can be expected on Monday night. Wide receivers Ricky Pearsall and Jauan Jennings are back, as is tight end George Kittle.
The news isn’t so good for San Francisco on the other side of the ball. With Nick Bosa and Fred Warner out for the year, the 49ers defense has struggled. In the EPA, San Fran is No. 31 in the NFL in defensive success rate. 114 points have also been achieved in the past four matches. Carolina’s offense may not be anything special, but it should play with some confidence after Bryce Young went wild in an overtime win over Atlanta in Week 11 (448 yards and three touchdowns). Now he faces a Niners defense that ranks second-to-last in passing defense (254.5 yards per game) and No. 25 in yards per pass attempt allowed (7.6). Heading into Week 12, no team had surrendered the over more than the 49ers. They are 7-3-1 O/U. The over is also 11-4 in the Panthers’ last 15 road games dating back to the 2023 season.
Carolina Panthers vs. San Francisco 49ers best player prop bet: Christian McCaffrey Over 42.5 receiving yards (-115)
McCaffrey is arguably the best passing RB in the NFL. The former Stanford standout has already made 74 receptions on 96 targets for 732 yards and five touchdowns. He was productive when Mac Jones was at QB for the 49ers, but he has an even better and more extensive rapport with Purdy. In three games with Purdy under center so far in 2025, McCaffrey is averaging 67 receiving yards and has scored two receiving touchdowns.
The former Panthers have exceeded that mark of 42.5 in 10 of 11 games this year, and his lowest performance is 40 yards. In fact, he has broken the 50-yard mark nine times and the 60-yard mark seven times. More of the same should continue against a Panthers defense that is allowing 212.8 yards per game and 7.2 yards per pass attempt (11th highest in the league). Carolina has given up the fourth-most catches to opposing RBs.
#Panthers #49ers #MNF #odds #preview #picks #predictions