Monday Night Football features a sneaky-interesting matchup as the Panthers head west as 7-point underdogs to face a 49ers offense that’s finally getting back to full strength.
My Panthers vs. 49ers predictions highlight value in the Carolina passing game, specifically a low line on their No. 2 option.
Read on for my NFL picks for Monday, November 24.
Panthers vs 49ers prediction
Panthers vs 49ers Best bet: Xavier Legette Over 24.5 receiving yards (-115)
Panthers vs 49ers MNF same-game parlay
It's a game with a 49.5-point total, and both of these teams were in shootouts last week where wide receivers went off. The only member that isn't included in this foursome that might have more passing yards is George Kittle, but this is a WR1+WR2 stack that is asking for Under 100 receiving yards combined for each team.
Panthers vs 49ers SGP
- Xavier Legette Over 24.5 receiving yards
- Ricky Pearsall Over 41.5 receiving yards
- Jauan Jennings Over 47.5 receiving yards
- Tetairoa McMillan Over 61.5 receiving yards
Our big-ticket SGP: TD Trio
George Kittle and Tetairoa McMillan are the two shortest non-RB TDs, and Legette was a legit target last week and caught a tuddy himself. Just remember, Brissett threw for almost 500 yards vs. the 49ers' defense last week and Brock Purdy and this offense still won 41-22.
Panthers vs 49ers SGP
- Xavier Legette anytime touchdown
- Tetairoa McMillan anytime touchdown
- George Kittle anytime touchdown
Panthers vs 49ers game predictions
Panthers vs 49ers moneyline prediction
I'm not 100% sold that this Carolina offense is the same one that we saw last week, but mid-offenses are putting up yards vs. the 49ers defense, and Carolina can flirt with 24 points. The question is whether the Panthers' defense can slow down a San Francisco offense that is almost back to full health and looked good even with Mac Jones. Before Week 11, this Carolina offense scored 13, nine, 16, and seven points. I think it's safe to put the 49ers in any ML parlays tonight.
Panthers vs 49ers spread prediction
This spread was 6.5 on the lookahead, hit 7 on Sunday night, and has bounced around from 6.5 and 7 all week. The flat-7 has been available all Thursday and all Friday, but there might be a tilt to the 7.5 on the weekend. Carolina is 2-1 ATS as a TD-or-more dog, but one of those was +7.5 in Week 2 vs the Cardinals. The 49ers were just 3.5-point favorites vs. the Cardinals on the road, and I don't see too much difference in Arizona and Carolina, while including the venue swap, which is less than 3 points. I'd rather have Carolina and the points.
Panthers vs 49ers Over/Under prediction
This is the highest total the Panthers have seen all year, and don't forget the Falcons were coming back from Germany when they lost in OT last week to the Panthers. If the Panthers are forced to pass and play from behind, I'd like a live Over at around 50 points, but if this game is close, Carolina might slow it down as they rank 30th in pass rate over expected. I like the Under here that was 45.5 on the lookahead.
Panthers vs 49ers odds
- Spread: Panthers +7 | 49ers -7
- Moneyline: Panthers +290 | 49ers -370
- Over/Under: Over 49.5 | Under 49.5
Panthers vs 49ers betting trend to know
The Panthers are 9-2 ATS historically in San Francisco. Find more NFL betting trends for Panthers vs. 49ers.
How to watch Panthers vs 49ers
| Location | Levi's Stadium, Santa Clara, CA |
| Date | Monday, November 24, 2025 |
| Kickoff | 8:15 p.m. ET |
| TV | ESPN |
Learn how to live stream Panthers vs. 49ers for free.
Panthers vs 49ers latest injuries
Panthers vs 49ers weather
Tonight’s showdown between the Panthers and Niners in Santa Clara will be played in crisp but comfortable conditions. Temperatures are expected to be in the upper 50s°F at kick off, dropping into the low 50s and eventually around 49–50°F by the late fourth quarter. Winds look light and not especially gusty, and with “mostly clear” conditions in the evening hours, rain and visibility issues are not in the picture. Fans will want a light jacket or hoodie, but from a pure weather standpoint, this is close to ideal November football.
Because the weather is so benign, it’s unlikely to become a major X-factor, which generally favors the better-rounded roster and the more precise passing offense. With no rain, no significant wind, and a dry field, quarterbacks on both sides should be able to drive the ball outside the numbers, and kickers shouldn’t face unusual difficulty on field goals or punts.
The cool air can make the ball a bit firmer and slightly affect distance on deep kicks and long throws, but the impact is marginal compared to windy or wet conditions. In short, don’t expect the elements to level the playing field; instead, execution, pass protection, and red-zone efficiency should decide this one far more than anything happening in the sky.
Monitor gametime conditions with our live NFL weather info and learn how weather impacts NFL betting.
More Panthers vs 49ers predictions and odds from Covers
- Panthers vs. 49ers props
- Panthers vs. 49ers same-game parlay
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- Panthers vs. 49ers anytime touchdown scorer picks
- Christian McCaffrey odds and props
- Monday Night Football odds
Odds are correct at the time of publishing and are subject to change.
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