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The Los Angeles Rams will hit the road to face the San Francisco 49ers on Monday Night Football. The Rams are 2-1 overall and 1-0 on the road this season, with Los Angeles coming off a 20-12 win over Arizona last week. The 49ers are 1-2 to begin the 2022 season, including an 11-10 loss to Denver in Week 3. The division-rivals are also participating in a rematch of last season's NFC Championship Game, with the Rams overcoming a 10-point deficit on the way to a win and an eventual Super Bowl title. 

Kick-off is at 8:15 p.m. ET in San Francisco. Caesars Sportsbook lists the 49ers as two-point home favorites, while the over/under, or total number of points Vegas thinks will be scored, is 42.5 in the latest 49ers vs. Rams odds. Before making any Rams vs. 49ers picks and NFL predictions, you need to see what SportsLine expert Tom Fornelli has to say.

The CBS national writer went a profitable 29-16-1 in his last 46 NFL picks. What's more, he has demonstrated a particularly sharp eye for the 49ers. In fact, Fornelli has gone a stunning 17-6 on picks involving San Francisco. Anyone who has followed him is way up.

Now, Fornelli has set his sights on Rams vs. 49ers and just locked in his picks and MNF predictions. You can head to SportsLine to see his picks. Now, here are several NFL odds and betting lines for Rams vs. 49ers:

  • 49ers vs. Rams spread: 49ers -2
  • 49ers vs. Rams over/under: 42.5 points 
  • 49ers vs. Rams money line: 49ers -130, Rams +110 
  • LAR: Rams are 11-13 against the spread in their last 24 games 
  • SF: 49ers are 13-10 against the spread in their last 23 games 
  • 49ers vs. Rams picks: See picks here
Featured Game | San Francisco 49ers vs. Los Angeles Rams

Why the Rams can cover

Los Angeles has strengths on both sides of the ball that should play well in this matchup. The Rams are in the top five in third down offense this season, moving the chains on 48.4% of chances, and Los Angeles has a dynamite passing connection with Matthew Stafford and Cooper Kupp. Stafford is No. 2 in the NFL in pass completion rate (72.5%) this season, and Kupp leads the NFL with 28 receptions. Kupp also sat atop the league leaderboard in receptions, receiving yards, and receiving touchdowns last season, and exceeded 100 receiving yards in each of three tilts against San Francisco.

On defense, the Rams are opportunistic this season, forcing seven turnovers in three games, and Los Angeles is giving up only 3.8 yards per carry and less than 100 rushing yards per game in 2022. Aaron Donald is the team's anchor with five straight seasons featuring double-digit sacks, and the 49ers are No. 24 or worse among NFL teams in scoring offense, total offense, passing offense, and passing touchdowns this season.

Why the 49ers can cover

In front of a raucous home crowd, San Francisco's defense projects to be effective in this matchup. Los Angeles is No. 25 in total yards and No. 28 in turnovers on offense, with bottom-five marks in rushing yards and yards per carry. The 49ers are off to arguably the best defensive start of any team in the league, allowing only 12.3 points per game and 0.91 points per drive. San Francisco is No. 2 in total defense, giving up only 227 yards per game, and lead the NFL in yards per drive, first downs allowed, opponent yards per play, opponent punt rate, passing yards allowed, and passing touchdowns allowed.

The centerpiece of the team's defensive attack is two-time Pro Bowl defensive end Nick Bosa, who leads the NFL in quarterback hits this season. Bosa has the most quarterback hits and tackles for loss of any player since the beginning of the 2021 campaign, and he already has four sacks and 14 pressures through three weeks.

How to make 49ers vs. Rams picks

Fornelli has analyzed this matchup and while we can tell you he's leaning Under on the point total, he has also discovered a critical X-factor that has him jumping all over one side of the spread. He's only sharing what it is, and which side to back, at SportsLine.

Who wins Rams vs. 49ers on Monday Night Football? And which critical X-factor makes one side of the spread a must-back? Visit SportsLine now to see which side of the Rams vs. 49ers spread to back, all from the expert who is an incredible 17-6 on picks involving San Francisco, and find out.