Panthers vs. 49ers Final Score Prediction for NFL Week 12 (Trust San Francisco?)

Brock Purdy is back, and the San Francisco 49ers are 7-4 this season after blowing out the Arizona Cardinals in Purdy’s third start of the 2025 season.

With his turf toe injury hopefully past him, Purdy is looking to lead the 49ers to a playoff berth and will take on another postseason contender in the NFC on Monday night in Week 12.

The Carolina Panthers and Bryce Young upset the Atlanta Falcons on Sunday last week, moving to 6-5 in the 2025 season. They entered Week 12 just a half-game back of the Tampa Bay Buccaneers in the NFC South.

Still, oddsmakers have set the Panthers as sizable underdogs on the road in this Monday Night Football clash.

All season long, the SI Betting team is sharing final score predictions for every NFL game, and this week is no different. Our goal is to give bettors an interesting take on the game’s score to help them decide on their spread and total bets.

Here’s my prediction for this primetime matchup in Week 12.

Panthers vs. 49ers Odds, Spread and Total

Odds via DraftKings Sportsbook.

Spread

Panthers +7 (-110)
49ers -7 (-110)

Moneyline

Panthers: +275
49ers: -345

Total

48.5 (Over -112/Under -108)

The odds for this game have held pretty steady with Brock Purdy back at quarterback for the 49ers, as they opened as seven-point favorites in this matchup.

Carolina has overachieved so far in 2025, sitting at 6-5 through 11 weeks, and it’s 6-3 against the spread as an underdog. Meanwhile, the 49ers are 2-1 in Purdy’s starts, moving to 7-4 with their win over the Arizona Cardinals in Week 11.

Panthers vs. 49ers Final Score Prediction

Earlier this week, SI’s NFL betting insider Iain MacMillan shared his favorite bet for this game in his Road to 272 column, and he’s back San Fran to cover:

I don't care that the Panthers continue to find ways to win games; I'm going to continue to bet against them. They're 26th in total DVOA, 26th in net yards per play, 26th in EPA per play, and 24th in opponent EPA per play. Meanwhile, they'll face a 49ers team that is starting to get healthy and whose offense looked rejuvenated with Brock Purdy back under center in Week 11 against the Cardinals.

It's time to buy in on the 49ers, and this is an extremely favorable matchup against a Panthers team who is worse than their record indicates. I'll lay the points with San Francisco on Monday Night Football.

San Francisco appears primed to make a playoff push down the stretch of this season with Purdy back, and the Panthers still have a lot of questions on offense (26th in EPA/Play) this season.

I agree with MacMillan and expect the 49ers to win this game by a wide margin.

Final Prediction: 49ers 27, Panthers 17

Odds refresh periodically and are subject to change.

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