On Monday Night Football, the San Francisco 49ers will host the Carolina Panthers in a matchup that promises excitement as both teams aim to build a winning streak. The game kicks off at 8:15 p.m. ET from Levi’s Stadium in Santa Clara, California, and will be a crucial contest in the NFC standings. The 49ers currently hold a 7-4 record and sit seventh in the NFC, while the Panthers are just behind at 6-5, ranked ninth. Both teams have shown inconsistency recently, alternating wins and losses over their past several games, making this a pivotal moment for either side to gain momentum.
San Francisco enters this game coming off a strong 41-22 victory against the Arizona Cardinals in Week 11. That performance was a marked improvement for the 49ers’ offense, which had been averaging just 22 points per game before lighting up the scoreboard against Arizona. Carolina, meanwhile, is coming off a thrilling 30-27 overtime win against the Atlanta Falcons on Sunday. The Panthers have also alternated wins and losses throughout their last five games, so both teams will be eager to string together consecutive victories on Monday night.
In terms of injuries, the Panthers will be without a few key players. Linebackers Christian Rozeboom (hip/hamstring) and Trevin Wallace (shoulder), along with center Cade Mays (ankle), will not play. The 49ers are also missing some personnel, with kicker Eddy Pineiro (hamstring) and linebacker Tatum Bethune (ankle) ruled out. These absences could affect the depth and special teams on both sides, though the core of each team remains intact.
The 49ers have had the upper hand in recent meetings between these two franchises, winning the last two encounters, including a matchup in 2022. San Francisco is currently favored by 7.5 points in the betting odds, with an over/under total points line set at 49.5. Money line odds favor the 49ers heavily at -395, while the Panthers are listed at +305. This point spread and total scoring line reflect expectations for a competitive game but one where San Francisco is viewed as the stronger team, especially playing at home.
One of the key storylines for this game is the matchup between Carolina’s offense and San Francisco’s defense. The Panthers’ young quarterback Bryce Young has been impressive this season, especially against the spread. Over his last nine starts, Young has gone 7-2 ATS, showcasing his ability to keep the Panthers competitive. Carolina’s offense has also been effective against NFC opponents this season, covering the spread in five of six such games in 2025. Young should find some comfort in facing a 49ers defense that has struggled to pressure the quarterback and create turnovers. San Francisco ranks last in the NFL in sacks and is near the bottom in interceptions, which could give Young the time and space he needs to make plays.
Carolina also has a strong running game to complement Young’s passing. Running back Rico Dowdle ranks fourth in the league in rushing yards, providing a balanced offensive attack that can keep defenses off balance. This dual-threat capability could pose problems for the 49ers, particularly given San Francisco’s recent issues with giveaways. At Levi’s Stadium this year, the 49ers have committed eight turnovers while only forcing one takeaway, suggesting that their home-field advantage may not be as significant as usual.
On the other side of the ball, San Francisco’s offense has shown signs of resurgence with Brock Purdy back to full health. Purdy’s return has energized the 49ers’ attack, highlighted by the 41-point outburst last week. Christian McCaffrey remains the centerpiece of the offense, leading the NFL in scrimmage yards and on pace for 1,000-yard seasons both rushing and receiving. His versatility makes San Francisco’s offense particularly difficult to defend.
Additionally, tight end George Kittle has been a major contributor since returning from injured reserve. Kittle has scored four touchdowns in his last four games, providing a reliable target for Purdy and adding another dimension to the offense. In contrast, the Panthers’ offense ranks near the bottom in several key categories, including scoring (28th in the NFL), passing offense, third-down efficiency, and yards per play. This disparity suggests that San Francisco may have the edge offensively, especially at home.
From a betting perspective