The NFL continues on Sunday, October 9, when we have plenty of games in Week 5, including this NFC duel, and here you can read the best 49ers vs. Panthers betting pick and odds.

San Francisco is looking for the first road victory of the season when they visit Carolina at Bank of America Stadium. The 49ers are -6.5 favorites on BetOnline Sportsbook, while the total is set at 39 points. These NFC rivals haven’t met since 2019.

49ers beat the reigning champions at home

The San Francisco 49ers (2-2) recorded their second home win of the season as they beat the divisional foes Los Angeles Rams 24-9. It was a defensive masterclass from defensive coordinator DeMeco Ryans, and even though the Rams had 21 first downs opposite San Francisco’s 13 and more than nine minutes of possession, the Niners managed to win thanks to sturdy D. The game was settled midway through the fourth quarter when Talanoa Hufanga returned an interception for a 52-yard touchdown.

Jimmy Garoppolo completed 16 of 27 passes for 239 yards and one touchdown. Deebo Samuel was a monster in this one and caught that lone TD pass from Jimmy G but also led the team with 115 yards on six receptions. San Francisco was solid on the ground, particularly Jeff Wilson Jr, who collected 74 rushing yards and a touchdown on 18 attempts. The 49ers had seven sacks opposite Los Angeles’ zero; Samson Ebukam and Nick Bosa got two apiece, while Dre Greenlaw led all the defenders with game-high 15 tackles.

T Trent Williams (ankle) and LB Azeez Al-Shaair (knee) are out indefinitely. DT Arik Armstead (foot), DT Javon Kinlaw (knee), and WR Jauan Jennings (ankle) are questionable to face the Panthers on Sunday.

Panthers’ poor offense cost them against the Cardinals

The Carolina Panthers (1-3) got to play three consecutive games at home, but after winning the first one over the New Orleans Saints, they lost 26-16 to the Arizona Cardinals. Carolina had a 10-3 lead at halftime, but it was all Arizona later as the Cards scored 23 points in the second half. Carolina’s offense was disappointing; the hosts were inferior in total yards (220-338), first downs (11-20), and possession (21:25- 38:35), while they also committed three turnovers opposite Arizona’s one.

Baker Mayfield was awful as he completed 22 of 36 passes for 197 yards, one touchdown, and two interceptions. Christian McCaffrey was on the receiving end of that TD pass; he end the game with 81 yards on nine catches. However, the run offense didn’t work as the Panthers had just 40 yards on 13 carries. On defense, Frankie Luvu had another impressive display as he returned an interception for a TD and registered a game-high 11 tackles.

QB Sam Darnold (ankle), WR Andre Roberts (knee), and S Jeremy Chinn (hamstring) are out indefinitely. WR Laviska Shenault Jr. (hamstring) is questionable to play on Sunday.


San Francisco:

  • 3-14 ATS in the last 17 games against Carolina
  • 4-8 ATS in the last 12 games against the NFC South rivals


  • 7-1 ATS in the last eight games when playing at home against San Francisco

San Francisco 49ers vs. Carolina Panthers Pick  

San Francisco has the best team defense in the NFL. The Niners are the second-best in pass defense and the best in run defense, so the Panthers will have a lot of work to do to penetrate through it and move the chains. Luckily for the hosts, the 49ers’ offense is among the worst with just 17.8 ppg on average, and we know that Carolina is capable of playing a sturdy defense at home. I don’t expect much from Baker Mayfield or Jimmy Garoppolo, but I do from Christian McCaffrey. The Niners are closer to the win here, but I am backing the hosts to cover and stay close.

Pick: Take the Panthers at +7.5 (-135)

The Total

I personally don’t like such low totals, and although I am well aware that San Francisco and Carolina are not high-scoring teams and are relying on their defenses to win games, I am going with Over. Something is telling me that we will have defensive or special teams touchdowns here, which will change the course of the game and take it to 40+ points. The total has gone Over in 14 of Carolina’s last 19 games against San Francisco, while the total went Over in 14 of Carolina’s previous 18 games against the NFC West opponents.

Pick: Go Over 38.5 points (-120)