The Carolina Panthers head to California to face the San Francisco 49ers on Monday night. Carolina has been on a roll and my early Panthers vs. 49ers predictions are betting on the visitors to keep things close in this Week 12 showdown.
Here are my NFL picks on the spread and total for this Monday Night Football clash on November 24.
Panthers vs 49ers predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Enjoying Covers content? Add us as a preferred source on your Google account
Early MNF spread pick: Panthers +6.5
The San Francisco 49ers are 7-4 and are just a game and a half behind the first-place Rams in the stacked AFC West.
Quarterback Brock Purdy and wide receiver Ricky Pearsall returned to the lineup after a six-week absence last week with San Fran cruising to a 41-22 win against the Cardinals.
While the Niners are third in the league in offensive success rate, they rank just 30th in defensive success rate. They allowed Arizona's backup QB Jacoby Brissett to throw for 452 yards last week despite missing his top WR in Marvin Harrison Jr.
Now they face the Carolina Panthers, who fought back from a 21-7 deficit to beat the Falcons in overtime last week with Bryce Young throwing for a career-high 448 yards.
The first pick in the 2023 draft, Young, seems to be growing as a passer. Along with the emergence of running back Rico Dowdle and rookie wideout Tetairoa McMillan, Carolina's offense ranks a respectable 14th in success rate.
The Panthers have been even more impressive on the other side of the ball, ranking eighth in defensive success rate. The Panthers are 5-2 straight up and against the spread in their last seven games, and with their balance on both sides of the ball, I'll take them with the points in Week 12.
Early MNF total pick: Over 48.5
Season-ending injuries to All-Pro linebacker Fred Warner and Pro Bowl edge Nick Bosa have caused the 49ers' pass defense to collapse. They are 24th in the league in coverage grade per PFF while ranking dead-last in pressure rate.
The Panthers had been heavily reliant on running the ball with Dowdle. However, we saw them air out the ball last week when they were playing from behind.
The Niners are 6.5-point home favorites, and I expect them to get out to an early lead, which should result in another high-volume passing game for Carolina.
While San Francisco has a struggling defense, it also has a highly efficient offense that is practically at full strength after getting back Purdy and Pearsall. With that explosive attack and shaky defense the Over has gone 6-1-1 in San Francisco's last eight games.
Panthers vs 49ers odds
- Panthers vs. 49ers spread: 49ers -6.5 (-120)
- Panthers vs. 49ers moneyline: Panthers +260, 49ers -320
- Panthers vs. 49ers Over/Under: 48.5
How to watch Panthers vs 49ers
- Panthers vs. 49ers matchup
- Date: Monday, November 24, 2025, 8:15 p.m. ET
- City: Santa Clara, CA
- Venue: Levi's Stadium
- TV: ESPN
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
Affiliate Disclosure: Our team of experts has thoroughly researched and handpicked each product that appears on our website. We may receive compensation if you sign up through our links.
