The San Francisco 49ers head to North Carolina for a showdown with the Carolina Panthers at Bank of America Stadium. It's time to continue our NFL odds series with a 49ers-Panthers prediction and pick.

The 49ers are coming off a significant 24-9 victory over the Los Angeles Rams on Monday Night Football. Jimmy Garoppolo completed 16 of his 27 passes for 239 yards, one touchdown, and no interception. Also, Jeff Wilson rushed 18 times for 74 yards and a touchdown at a 4.1 yards-per-carry rate. Deebo Samuel caught six passes for 115 yards and a touchdown while rushing twice for two yards. Brandon Aiyuk caught four passes for 37 yards, while George Kittle caught two passes for 24 yards. 

The Panthers lost 26-10 to the Arizona Cardinals. Baker Mayfield completed 22 of his 36 passes for 197 yards, one touchdown, and two interceptions. He took two sacks and once again struggled to move the chains. Christian McCaffrey rushed eight times for 27 yards while also catching nine passes for 81 yards and a touchdown. Also, D.J. Moore caught six passes for 59 yards. Carolina struggled on third downs, going 2 for 10. Moreover, they also could not hold onto the ball, committing three turnovers. 

The Panthers lead the all-time series 13-8. However, these teams had not met since 2019, when the 49ers smashed the Panthers 51-13 at Levi Stadium. Garoppolo completed 18 of his 22 passes for 175 yards, two touchdowns, and an interception in that game. Moreover, he took three sacks. The 49ers recently brought back Tevin Coleman as an extra running back. Coincidentally, his back game came against the Panthers in that matchup. He rushed 11 times for 105 yards and three touchdowns.

Additionally, Wilson rushed twice for six yards. Kittle was spectacular, catching six passes for 86 yards. Meanwhile, Samuel added three catches for 19 yards, two rushes for 29 yards, and a touchdown. The defense dominated, with Nick Bosa sacking the quarterback three times. 

The Panthers did not produce much offense. Conversely, it was McCaffrey doing the heavy lifting. He finished with 14 rushes for 117 yards and a touchdown with four catches for 38 yards. 

Here are the 49ers-Panthers NFL odds, courtesy of FanDuel. 

NFL Odds: 49ers-Panthers Odds

San Francisco 49ers: -6.5 (-110)

Carolina Panthers: +6.5 (-110)

Over: 39.5 (-110)

Under: 39.5 (-110)

Why The 49ers Could Cover The Spread

The 49ers have the offensive firepower to destroy Carolina. However, will it be enough after having endured a shorter week due to Monday Night Football? 

Garoppolo has a 93.2 passer rating since taking over for an injured Trey Lance. Subsequently, he has 604 yards, three touchdowns, and one interception through three games. Wilson has shouldered the load at running back since the injury to Elijah Mitchell. He has rushed 57 times for 255 yards and a touchdown while catching seven passes for 58 yards. Meanwhile, Samuel has caught 18 passes for 246 yards with two touchdowns while also rushing 19 times for 113 yards and a touchdown. Aiyuk has caught 14 passes for 179 yards and a touchdown, while Kittle has caught six passes for 52 yards. However, Kittle has not scored yet and is still searching for his first touchdown. 

The defense is one of the best in the NFL. Bosa has 12 solo tackles and six sacks. Meanwhile, Talanoa Hufanga continues to play at an elite level, recording 20 solo tackles with two interceptions, including an interception return for a touchdown against the Rams on Monday. Fred Warner has 15 solo tackles, while Dre Greenlaw has 26. 

The 49ers have excelled when they have run the ball well and stopped the run. Moreover, it also helps when they do not make mistakes. They must learn how to play better in the second half of games. The offense has scored 16 points through four games for a pitiful four points per game. It is a significant reason for their 2-2 record, as they held leads in both losses.

The 49ers must adjust at the half and do better to score more in the final two quarters. The 49ers will cover the spread if they can move the chains through the ground and free up the offense. Likewise, the defense must remain efficient and stop McCaffrey. 

Why The Panthers Could Cover The Spread

Mayfield has not been good, as he has sported a 75.0 passer rating with 747 yards, four touchdowns, and three interceptions. Likewise, he has also taken 11 sacks. McCaffrey remains the heart of the offense. He has rushed 58 times for 270 yards and a touchdown while also catching 19 passes for 138 yards and a touchdown. 

The defense has some playmakers that give the Panthers hope. Shaq Thompson has 15 solo tackles, while Brent Burns has 13 solo tackles and three sacks through four games. Additionally, Jaycee Horn has nine solo tackles and an interception. 

The best way to beat the 49ers is to stop their ground attack and force Garoppolo to throw. The Panthers will cover the spread if McCaffrey can move the ball and Mayfield avoids mistakes. Additionally, the defense must contain Wilson and cannot let Samuel burn them. 

Final 49ers-Panthers Prediction & Pick

The 49ers have not fared well against the Panthers historically. Additionally, they are coming off a Monday Night game. It will not be the blowout many are predicting, but the 49ers still may cover by inches. The 49ers will cover the spread, likely winning by seven. 

Final 49ers-Panthers Prediction & Pick: San Francisco 49ers: -6.5 (-110)