Here is the Pickwatch BetSmart Preview for the Carolina Panthers vs. San Francisco 49ers game in Week 12 of the 2025 NFL Season.

Carolina Panthers vs. San Francisco 49ers Game Info

Date: Monday, November 24 2025
Time: 8:15 PM ET
Location: Levi's Stadium — Santa Clara, California
TV: ESPN/ABC

Panthers vs. 49ers Betting Odds

Point Spread
- Panthers +7.5
- 49ers -7.5
Moneyline
- Panthers +320
- 49ers -370
Total
- Over/Under 49.5

Season Betting Records

Moneyline
- Panthers: 6-5
- 49ers: 7-4
Against the Spread
- Panthers: 7-4
- 49ers: 6-5
Totals (Over-Under)
- Panthers: 6-5
- 49ers: 7-3-1

Carolina Panthers (6–5) @ San Francisco 49ers (7–4) Preview

The Panthers visit San Francisco looking to make a playoff push with a challenging road trip ahead. Carolina’s offense has shown flashes—passing league average in EPA/play last week—but remains without consistency in the red-zone and has allowed 5+ turnovers in three of their last five games. Meanwhile, the 49ers are firing on all cylinders at home: averaging 29 points and giving up fewer than 17 over their past four home games.

San Francisco’s defense ranks top 3 in yards allowed and third-down conversion rate (~32 %) this season, which puts heavy pressure on Carolina’s offensive line and third-year QB Bryce Young to execute under duress. Carolina’s rush offense, led by young RB Rico Dowdle, must get going early to keep this from becoming a one-dimensional passing attack. The 49ers’ veteran offense—anchored by QB Brock Purdy and WR Deebo Samuel—will try to exploit Carolina’s linebacking depth and force mismatches.

As for injuries, San Francisco is managing WRs who are listed as limited this week (impacting depth) and the Panthers are missing one of their starting cornerbacks plus a top run-blocker on the interior line. These absences could slightly shift value in the spread or total markets.

The spread near –7.5 and total around 49.5 indicates the market expects the 49ers to control tempo and limit Carolina’s possessions. If the Panthers force turnovers or sustain long drives, the live value may shift toward Carolina +7.5 or the under in the total given San Francisco’s habit of early leads.

Panthers/49ers Head-to-Head (H2H) Stats and Analysis

The Carolina Panthers lead the all-time series 13–10 vs. the Carolina Panthers. Here are the last 5 meetings:

San Francisco 49ers 37, Carolina Panthers 15 — October 9, 2022
San Francisco 49ers 51, Carolina Panthers 13 — October 27, 2019
Carolina Panthers 23, San Francisco 49ers 3 — September 10, 2017
Carolina Panthers 46, San Francisco 49ers 27 — September 18, 2016
San Francisco 49ers 23, Carolina Panthers 10 — January 12, 2014

BetSmart Betting Rundown

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NOTE: All available bets are as of time of publication. Odds and lines change often, so be sure to check each subsequent Pickwatch betting tool for the latest numbers.

Arbitrage

Our Arbitrage Betting Tool is currently identifying 8 arbitrage betting opportunities for guaranteed profit.

Middles

Our Middle Betting Tool is currently identifying 60 middle betting opportunities.

Positive EV

Our Positive EV Betting Tool is currently identifying 18 different positive expected value wagers, and provided data on the expected value percentrage, and how often the bet has hit in the last 5, 10 and 15 games.

Player Props

Our Prop Finder Tool is currently identifying 272 different player prop bets, and provided data on how often each player has hit the specific prop in the last 5, 10 and 15 games.

Panthers vs. 49ers: Expert Picks

Visit our Expert Picks page to view picks and data from over 200 experts to see where the consensus is on the Panthers vs. 49ers moneyline, point spread and total points.