49ers vs. Rams Prediction: Thursday Night Football Odds & Expert Picks

The Los Angeles Rams welcome the San Francisco 49ers to SoFi Stadium for Thursday Night Football (8:15 p.m. ET, Prime Video), and my 49ers vs. Rams prediction takes stock of the pervading uncertainty hanging over the visitors' lineup. 

The Rams are the 5.5 to 6.5-point betting favorite with growing concerns over the 49ers' personnel issues. My NFL picks below, part of the NFL predictions for Week 5, provide analysis regarding recent injury reports while offering my best bets, including a Kyren Williams player prop. 

📊 49ers vs. Rams odds: Thursday Night Football

Latest Thursday Night Football odds update in real time.

🏈 49ers vs. Rams predictions: Thursday Night Football

NFL expert picks for Thursday Night Football; NFL odds subject to change.

• Game pick: Rams -5.5 (-122 via FanDuel) ⭐⭐⭐⭐
• Over/Under pick: Under 46.5 (-102 via FanDuel) ⭐⭐⭐⭐
• Player prop bet: Kyren Williams Over 16.5 carries (-111 via DraftKings) ⭐⭐⭐⭐

✅ 49ers vs. Rams expert pick for TNF

Track the latest NFL scores for line movement and matchup info.

⬇️ Rams -5.5 (-122) ⭐⭐⭐⭐

I hope you followed my against-the-spread pick in our 49ers vs. Rams early prediction, as that -3 spread is long gone. The uncertainty surrounding several key injured 49ers, including wide receivers Ricky Pearsall and Jauan Jennings, and QB Brock Purdy, has increased the spread to -5.5 or -6.5. 

Based on various reports, the general sentiment is that Jennings will play, with Purdy and Pearsall likely losing the race against time. If that comes to fruition, I'm comfortable with the Rams winning by at least six.

If not, I'm happy backing the Under on the 46.5-point total. 

A presumed Mac Jones-led offense devoid of tight end George Kittle, possibly Pearsall and Jennings, won't cause any sleepless nights for a Rams defense that has the eighth-best EPA per play.  

With Jones at the helm, the 49ers' offense struggled to produce against an average Arizona Cardinals defense, scoring their only touchdown in the fourth quarter. 

Jones isn't far removed from a recent knee injury, providing more reason to back the Rams. On the opposing side, Rams QB Matthew Stafford will look forward to facing a 49ers defense that doesn't have Nick Bosa at its disposal.

Of the best sports betting sites, FanDuel is the only one offering -5.5. And it might not last long. 

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💰 49ers vs. Rams player prop bet for TNF

Our NFL player prop odds tool shows the best odds for every market across legal sportsbooks in your area.

⬆️ Kyren Williams Over 16.5 rushing attempts (-111) ⭐⭐⭐⭐

Such is the uncertainty surrounding who will or won't play, there are currently no 49ers' receiver props available at the best sports betting apps. Keep your eye on that market in the lead-up to kickoff, as running back Christian McCaffrey should receive an increased target share in the passing game.

Of course, the extent of which depends on Pearsall and Jennings' participation. So, it's on to Kyren Williams, who I expect to be a focal point of the Rams offense to an even higher degree than usual.

The Rams will want to control the clock and tempo. I believe Los Angeles will be protecting a decent lead in the fourth quarter, creating ripe conditions for an increased number of carries. He hit the Over on this total in three of four games, averaging 17 carries. 

DraftKings' -111 odds present the best value, with BetMGM (-135) providing the worst possible return. A winning $10 bet at DraftKings would yield a profit of $9.01.

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