The Carolina Panthers will take on the San Francisco 49ers in a Monday Night Football NFL Week 12 matchup at Levi’s Stadium, scheduled to commence at 8:15 p.m. EST.

All week, the narrative surrounding this primetime clash has focused on the “Revenge Game” for 49ers star Christian McCaffrey against his former team, as well as the sudden surge of Panthers quarterback Bryce Young. Young is coming off a franchise-record performance where he threw for 448 yards against the Falcons, while McCaffrey leads the NFL in scrimmage yards entering Week 12.

Fortunately for football fans, it has now been confirmed that both quarterbacks are fully healthy for this showdown; Bryce Young (ankle) and Brock Purdy (toe) were full participants in practice to close the week and carry no injury designations.

However, the Panthers’ defense has taken a significant hit. The official injury report confirms that Carolina will be without key linebackers Christian Rozeboom (hip/hamstring) and Trevin Wallace (shoulder), who have both been ruled OUT. This is a critical development for a defense tasked with stopping McCaffrey.

On the San Francisco sideline, special teams will be affected as kicker Eddy Pineiro (hamstring) has also been ruled OUT, while defensive lineman Robert Beal Jr. is listed as doubtful.

In light of these confirmed absences in the Panthers’ front seven and the 49ers’ special teams unit, the data analysts at Dimers updated their Panthers vs. 49ers score prediction and player stat projections.

The results of Dimers’ simulations were compared to updated sportsbook odds to compile the data-driven Panthers-49ers preview below.

Panthers vs. 49ers betting preview

Utilize the interactive widget below to discover the latest spread, total, and moneyline odds and probabilities for the Panthers-49ers game at Levi’s Stadium.

Check out all the important details on today’s game, as well as the best odds sourced from the top sportsbooks in the country.

Game details

The key information you need before the Panthers vs. 49ers NFL game.

Teams: Carolina Panthers vs. San Francisco 49ersDate: Monday, November 24, 2025Kickoff: 8:15 p.m. ESTLocation: Levi’s StadiumNFL standings: Current NFL division standingsNFL injuries: Check the latest updates to the official NFL injury reportOdds

The latest and best odds for the NFL showdown between the Panthers and 49ers.

Spread: Panthers +7.5 (-112), 49ers -7.5 (-102)Moneyline: Panthers +330, 49ers -375Total: Over/Under 49.5 (-110/-106)

The odds and lines presented in this article are the best available from selected sports betting sites at the time of publication and are subject to change.

Fans of both teams can unlock betting bonuses with the Thanksgiving Week betting promos from DraftKings, BetMGM, and FanDuel, while Bet365’s $150 sign-up offer has emerged as the most popular NFL betting deal among local fans in North Carolina.

Expert prediction: Panthers vs. 49ers

Using advanced data analysis and machine learning, the experts at Dimers have performed 10,000 simulations of Monday’s Panthers vs. 49ers game.

According to Dimers’ popular predictive analytics model, the 49ers are more likely to defeat the Panthers at Levi’s Stadium. This prediction is based on the model giving the 49ers a 75% chance of winning the game.

Elsewhere on the betting board, Dimers predicts that the bookmakers have gotten it right and the Panthers and 49ers each have a 50% chance of covering the spread, while the over/under total of 49.5 points is also considered an equal 50-50 chance of hitting.

As always, these predictions and probabilities are correct at the time of publication but are subject to change.

Panthers vs. 49ers best bet

Our top pick for the Panthers vs. 49ers Week 12 NFL matchup is to bet on the Panthers moneyline (+330).

This expert betting advice is formulated through cutting-edge modeling and valuable wagering intelligence, designed to bring you the best possible plays.

While the 49ers are more likely to win the game, according to Dimers, taking the Panthers moneyline is the best option due to the 2.2% edge identified when comparing Dimers’ data-driven probabilities to the betting odds.

Score prediction for Panthers vs. 49ers

Dimers’ projected final score for the Carolina vs. San Francisco game on Monday has the 49ers winning 28-21.

This expert prediction is based on each team’s average score following 10,000 game simulations, offering a glimpse into the potential outcome.

Carolina Panthers stat projections:First touchdown scorer predictionsRico Dowdle: 11.8% probabilityTetairoa McMillan: 7.3% probabilityXavier Legette: 3.9% probabilityAnytime touchdown predictionsRico Dowdle: 50.4% probabilityTetairoa McMillan: 35.2% probabilityXavier Legette: 20.8% probabilityProjected box score leadersQB passing yards: Bryce Young, 214 yardsReceiving yards: Tetairoa McMillan, 68 yardsRushing yards: Rico Dowdle, 77 yardsSan Francisco 49ers stat projections:First touchdown scorer predictionsChristian McCaffrey: 18.9% probabilityGeorge Kittle: 8.8% probabilityJauan Jennings: 6.2% probabilityAnytime touchdown predictionsChristian McCaffrey: 69.1% probabilityGeorge Kittle: 42.1% probabilityJauan Jennings: 32.0% probabilityProjected box score leadersQB passing yards: Brock Purdy, 255 yardsReceiving yards: George Kittle, 57 yardsRushing yards: Christian McCaffrey, 73 yardsNFL Week 12: Panthers vs. 49ers

Get ready for Monday’s game between the Panthers and 49ers in Week 12 of the NFL season at Levi’s Stadium, which is scheduled to start at 8:15 p.m. EST. We emphasize that all of the NFL predictions and NFL best bets in this article are based on 10,000 data-driven simulations of the Panthers vs. 49ers matchup, and they are accurate at the time of publishing. They are intended to assist you make more informed choices when placing bets at online sportsbooks.

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