San Francisco 49ers running back Christian McCaffrey (23) celebrates after scoring a touchdown during a week 9 game between New York Giants and San Francisco 49ers at MetLife Stadium on Sunday, Nov. 2, 2025.

We’re heading into the second half of the NFL season, and whether you’re up or down, you need to know what the best (and worst) bet of the week is. Heading into week 10, there are a slew of games to comb through, but we have you covered.

Here is my best bet of the week and the game you need to stay away from.

Best Bet: San Francisco 49ers (+4.5) vs. Los Angeles Rams (-5.5)

Don’t let the narrative fool you here. On paper, the Rams are red hot and playing the best football in the league, and the San Francisco 49ers are injured with question marks throughout the lineup. Even if that might be the case, Kyle Shanahan always brings his A-game when matching up with old colleague and friend Sean McVay. The Rams and Niners rivalry has defined the NFC West for the past decade, and regardless of the strength of the two sides, Shanahan has never rolled over for the Rams.

Earlier this season, the Niners stole a win over the Rams when they were even more banged up, and that was spearheaded by a beautifully crafted opening drive from Shanahan to get his team momentum early. If this were a straight moneyline, I might waver on picking the Niners, but giving over a field goal to the Niners when the Rams have one of the worst special teams in the league is too much.

These two teams always play close, and with home-field advantage, I love the Niners here.

Worst Bet: New Orleans Saints (+5.5) vs. Carolina Panthers (-5.5)

Stay away from this game. The Saints looked awful last week against the Rams, and the Panthers shocked the Packers, but don’t fall into the trap. Saints have hung around most games this year, and Tyler Shough wasn’t awful versus a top-ranked Rams defensive line. The Panthers are an enigma that seems to do better when Bryce Young plays poorly. Throw in that this is a division game, and the Saints are playing with house money and nothing to lose while the Panthers are seeing the light at the end of the tunnel for the first time in years, and this is a game I’d stay away from.

I know the Saints are bad and already in 2026 mode, but I can’t trust the Panthers with this wide of a spread. Not yet.

All lines are provided from DraftKings

This article originally appeared on Touchdown Wire: The best and worst NFL bets for Week 10

Reporting by Tyler Erzberger, Touchdown Wire / Touchdown Wire

USA TODAY Network via Reuters Connect