by Rod Pearson
Friday, Nov 21, 2025
Game Time: 8:15 pm ET, Monday, November 24, 2025
Venue: Levi's Stadium, Santa Clara, CA
Where to Watch: ESPN
Opening Odds at USA Sportsbooks
DraftKings: Point Spread: Panthers +7, 49ers -7; Over/Under: 49.5 points
Bet365: Point Spread: Panthers +7, 49ers -7; Over/Under: 49.5 points
BetMGM: Point Spread: Panthers +7, 49ers -7; Over/Under: 49.5 points
Season Record
Carolina Panthers: 6-5 (2nd place, NFC South)
San Francisco 49ers: 7-4 (3rd place, NFC West)
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Recent Form
Carolina Panthers: won their last game on the road against the Atlanta Falcons 30-27 in overtime.
San Francisco 49ers: won their last game on the road against the Arizona Cardinals 41-22.
Carolina Panthers vs San Francisco 49ers Preview and Analysis
The Panthers are entering this game with a 6-5 record overall and they have a 2-1 record in their divisional games too. They are 3-2 in their home games, 3-3 in their road games, and they are also 0-0 in their neutral site games this season, but they will be on the road for this game. They won their last game against the Atlanta Falcons 30-27 in OT. Bryce Young was the starting QB and he completed 31/45 passes for 448 passing yards, 3 touchdowns, and 0 interceptions. Rico Dowdle led the team in rushing yards with 45. Tetairoa McMillan led the receivers with 130 receiving yards on 8 receptions and 2 TDs. Tre'von Moehrig led the defense in that game with 6 solo tackles and 5 assisted tackles while no one on the defense recorded a sack for them. No one on the defense came away with an interception for them in that one.
The 49ers are entering this game with a 7-4 record overall and they have a 4-1 record in their divisional games too. They are 2-2 in their home games, 5-2 in their road games, and they are also 0-0 in their neutral site games this season, but they will be at home for this game. They won their last game against the Arizona Cardinals 41-22. Brock Purdy was the starting QB and he completed 19/26 passes for 200 passing yards, 3 touchdowns, and 0 interceptions. Christian McCaffrey led the team in rushing yards with 81 and 2 TDs. George Kittle led the receivers with 67 receiving yards on 6 receptions and 2 TDs. Curtis Robinson led the defense in that game with 5 solo tackles and 6 assisted tackles while no one on the defense recorded a sack for them. Deommodore Lenoir and Malik Mustapha each came away with 1 interception for them in that one.
Panthers vs 49ers Prediction
The current betting odds have the 49ers listed as a 7 point favorite in this game according to Draftkings Sportsbook. The 49ers have looked really good in their games this season with their 7-4 record overall, but that record has them right near the bottom of the NFC West in a really competitive division. They aren't out of this division race though with their 4-1 divisional record in the NFC West. Meanwhile, the Panthers have looked good in their games this season with their 6-5 record overall which has them right near the top of the NFC South. They are off a 30-27 road win over the Falcons in their last one, but they lost at home to the Saints the week before and they have been really up and down all year. Bryce Young looked great in their win over the Falcons, but he has looked terrible in other games where they have relied more on the run. The 49ers have been dealing with a lot of injuries this season, but they are starting to get healthier now with a lot of their weapons coming back. Purdy also came back in their 41-22 win over the Cardinals last week and he looked great in that road game. The 49ers started slow, but they are starting to put things together now while the Panthers have been too inconsistent from week to week. The best way to place a bet here is on the 49ers to cover the spread in this game.
Panthers 49ers Prediction: Our NFL Pick for Monday, November 24, 2025 (8:15 pm ET start time) is 49ers 28 Panthers 10.
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NFL Betting Trends
Carolina Panthers: 30-21 ATS against NFC West division opponents. 30-23 ATS off an upset win as a road underdog. 3-0 OVER against NFC West division opponents. 7-4 OVER after 1 or more consecutive wins. 11-6 OVER versus poor defensive teams - allowing 5.65 yards/play or more.
San Francisco 49ers: 4-9 ATS as a home favorite of 7 points or less. 2-10 ATS in a home game where the total is greater than or equal to 45.5. 2-9 ATS after a game with a turnover margin of +2 or better. 28-18 OVER in all games. 12-5 OVER as a favorite of 3.5 to 9.5 points.
Key Injuries
Carolina Panthers: T. Wharton (DL) Injured - Knee. C. Rozeboom (LB) Injured - Hip. B. Young (QB) Injured - Ankle. X. Legette (WR) Injured - Hip. T. Wallace (LB) Injured - Shoulder. L. Ransom (S) Injured - Hand. T. McMillan (WR) Injured - Ankle.
San Francisco 49ers: T. Williams (OT) Injured - NIR-Rest. C. McCaffrey (RB) Injured - NIR-Rest. E. Pineiro (K) Injured - Hamstring. R. Beal Jr. (DL) Injured - Concussion. L. Gifford (LB) Injured - Hip. C. Robinson (LB) Injured - Elbow. B. Purdy (QB) Injured - Toe. D. Winters (LB) Injured - Knee. T. Bethune (LB) Injured - Ankle. R. Pearsall (WR) Injured - Knee.
Notable Quotes
“It's part of our identity; we embrace that. It's just resilience. We talk about it. Whatever it was, it's on to the next play.” - Bryce Young after their win against the Falcons in their last game.
“Coming in, I didn't want to think about (the toe) at all and I didn't. I just went out and played quarterback like I've always played. It feels great now.” - Brock Purdy after their win against the Cardinals in their last game.
Starting Lineups
Carolina Panthers
WR McMillan, Tetairoa
WR Tremayne, Brycen
WR Coker, Jalen
TE Tremble, Tommy
QB Young, Bryce
RB Dowdle, Rico
San Francisco 49ers
WR Pearsall, Ricky
WR Bourne, Kendrick
WR Jennings, Jauan
TE Kittle, George
QB Purdy, Brock
RB McCaffrey, Christian
FB Juszczyk, Kyle
Statistical Leaders
Carolina Panthers
Passing: Bryce Young (1,962)
Rushing: Rico Dowdle (833)
Receiving: Tetairoa McMillan (748)
Touchdowns: Rico Dowdle (6)
San Francisco 49ers
Passing: Mac Jones (2,151)
Rushing: Christian McCaffrey (707)
Receiving: Christian McCaffrey (732)
Touchdowns: Christian McCaffrey (11)
Coaches:
Carolina Panthers: Dave Canales (2nd season)
San Francisco 49ers: Kyle Shanahan (9th season)
Rod Pearson
About the Author:
Rod Pearson has been a rabid sports fan his entire life. He grew up in Ontario, and was skilled in both hockey and baseball, and pitched in an elite baseball league for many years. In 2022, Rod decided to hang up his glove, so that he could write about the sports he loves -- but from a gambling perspective. Join Rod every day as he breaks down the games to find the best betting value.
