49ers vs. Rams Point Spread: NFL TNF Week 5 Odds, Prediction
The 49ers dropped their first game of the year last week at home to the surging Jacksonville Jaguars, 26-21. Quarterback Brock Purdy returned to the lineup but struggled, throwing two interceptions and losing a fumble as San Francisco turned the ball over four times overall, and also allowed an 87-yard punt return for a touchdown in the defeat.
The Rams, meanwhile, scored two touchdowns in the final three and a half minutes of their game against the Indianapolis Colts to sneak away with a 27-20 triumph. Wide receiver Puka Nacua continued his torrid early-season run, catching 13 passes for a career-high 170 yards and a touchdown for Los Angeles.
Los Angeles has won three straight in this series, by a combined 10 points.
The Rams are seven-point favourites to win on the NFL odds, with the total pegged at 46.5.
NFL Point Spread and Betting Analysis
The Rams are 3-1 against the spread this season, including 3-0 as a favourite, and 2-0 at home. They are 4-1 ATS in their last five meetings with the Niners, who are 3-10 ATS in their previous 13 games overall.
Both teams have played twice to the Over, something they’ve done four of the last five times when playing each other in Los Angeles.
San Francisco 49ers
Defensive end Nick Bosa, who had two sacks in three games, is out for the year with a torn right ACL. This is the second time in his career that he’s missed the majority of a season after tearing an ACL, having already done so in 2020.
That is a devastating loss for the 49ers, as Bosa has averaged 12.5 sacks in his five full seasons. The 2022 NFL Defensive Player of the Year has led San Francisco in sacks each of the past four seasons.
The defence will need to overcome this loss, as the 49ers’ special teams is struggling, and the run game, tied for 30th at 3.3 yards per carry, is going nowhere fast. Christian McCaffrey is the only viable offensive threat currently.
Los Angeles Rams
Nacua’s knee injury in training camp last year nagged him all season, forcing him to miss several games. The third-year wide receiver is having no such issues four games into the 2025/26 campaign. According to ESPN Research, he became just the second player in NFL history to record 40+ receptions and 500+ yards through the first four games. Nacua did ding his thumb in the win over the Colts last week, but it was a momentary jolt, as he returned to complete his career-high 170-yard day.
Davante Adams, who also had a touchdown reception against Indianapolis, is listed as questionable with a testy hamstring. That development will be important to stay on top of, as Adams’ veteran presence has helped to allow Nacua to get off to such a hot start.
NFL Prediction: Who Will Win 49ers vs. Rams?
The 49ers are 2-0 on the road, and the Rams are 2-0 at home. Something has to give. Los Angeles is a blocked field goal kick away from being a perfect 4-0. Meanwhile, the 49ers have three wins by a combined 10 points. With so little margin for error, San Francisco cannot afford its current injuries.
Look for the Rams to cover the 5.5-point spread as favourites in a 28-21 victory.
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