49ers vs. Rams: Start 'Em, Sit 'Em

Fantasy football start 'em, sit 'em lineups advice for 49ers vs. Rams on Thursday Night Football in Week 5 (2025). NFL matchups analysis and TNF starts/sits.

If you didn't get your fill of NFC West football last Thursday night, I've got some good news for you! In Week 5, we get the other two teams in the division as the San Francisco 49ers travel to face the Los Angeles Rams. For fantasy football, some of the game's elite performers are suiting up in this contest, but there are also plenty of injury concerns to worry about for one side.

No matter what happens, this game features a matchup of the potential top running back in the league and the top wide receiver in the league. But with so many question marks due to potential injuries, it will be all the more important to make sure you are staying on top of inactives and late breaking news as this game gets closer to kicking off.

I will bring you Thursday Night Football analysis all season, focusing on who to start, who is on the fence, and who should be benched. Let's dive into this Week 5 Thursday night matchup for the 2025 season. You can also check out our main Week 5 start 'em, sit 'em matchups article for all other games. Good luck in your fantasy football week, RotoBallers!

• 2025 fantasy football rankings
• Running back (RB) fantasy football rankings
• Wide receiver (WR) fantasy football rankings
• Tight end (TE) fantasy football rankings
• Quarterback (QB) fantasy football rankings
• FLEX fantasy football rankings
• Defense (D/ST) fantasy football rankings
• Kicker (K) fantasy football rankings
• Dynasty fantasy football rankings

San Francisco 49ers @ Los Angeles Rams

Thursday, October 2, 8:15 PM ET

Notable Injuries:

• Brock Purdy (QB, SF) - OUT- Toe
• Ricky Pearsall (WR, SF) - OUT - Knee
• Jauan Jennings (WR, SF) - OUT - Ankle/Ribs
• Brandon Aiyuk (WR, SF) - OUT - Knee
• Tyler Higbee (TE, LAR) - Questionable - Hip

49ers vs. Rams Matchup Breakdown

The San Francisco 49ers and the Los Angeles Rams are both tied atop the NFC West at 3-1 heading into Week 5. But while the Rams seem to be improving each week, the 49ers are looking more like the walking wounded and just lost at home, 26-21, to the Jacksonville Jaguars. The story of this game will be the injuries to San Francisco, and whether they will impact its ability to keep this one close.

Primetime in LA.

🎟️: https://t.co/6r14urC6dR pic.twitter.com/ijjjKNx02C

— Los Angeles Rams (@RamsNFL) September 30, 2025

For San Francisco, it's not just offensive injuries, either. Nick Bosa has been placed on IR and will not play. The 49ers also have seven defensive players either listed "Out" or "Questionable" for Thursday Night Football. That's the reason why this spread is up to 6.5 points in favor of the Rams.

Both teams are top 10 in the NFL in yards per play allowed by their defense, as well as opponents' third-down conversion rate. The defenses, when healthy, are doing their job, so it all comes down to who takes the field for the 49ers on Thursday night.

If the San Francisco defense can come in healthy and put a lot of pressure on Matthew Stafford, he won't be able to wait for Puka Nacua or Davante Adams to open up away from their defenders. That's what will keep the 49ers in this game above everything else.

Must-Starts for Fantasy Football Lineups

Christian McCaffrey (RB, SF)

Christian McCaffrey is a must-start, of course, because of his massive volume in the rushing and the passing game. McCaffrey is No. 1 among running backs in weighted opportunities, targets, and receiving yards. The only crack in the armor this year is his rushing efficiency.

McCaffrey's true yards per carry number this year is 3.4 yards, which is just 47th among running backs. That can be attributed to a lot of things, like past injury, age, shaky line, etc. But he is just not hitting the holes with the burst he used to have several years ago. He will still get his fantasy points, but they will come thanks to volume instead of multiple explosive plays.

Ricky Pearsall (WR, SF)

UPDATE: Ricky Pearsall has been ruled out for Thursday

Through four weeks of the 2025 season, only McCaffrey is better than Ricky Pearsall in receptions and targets. Pearsall leads in receiving yards with 327, and has a 21% target rate. The big question, of course, is whether he will play in Week 5. If he does, the Rams are in the top 12 of most receiving yards allowed to the position, and Pearsall would be in line for a lot of work.

Ricky Pearsall Still Sidelined with Knee Injury on Tuesday https://t.co/pSn5vWGdQX

— RotoBaller NFL (@RotoBallerNFL) September 30, 2025

Puka Nacua (WR, LAR)

If you name a receiving statistic, Puka Nacua is probably the NFL leader in that stat. He only has one touchdown, but is No. 1 in receptions, yards, yards per route run, and a host of other numbers. Matthew Stafford looks his way early and often, and he has proved to be matchup-proof through these four weeks.

Davante Adams (WR, LAR)

Even with all the usage Nacua is seeing in this offense, Davante Adams is still putting up a fantastic fantasy season. Adams has a 26% target share, is ninth in air yards, fifth in targets, and is No. 1 in the NFL with eight red-zone targets. He is the touchdown scorer through the air for this Rams team and has a 47% target share in that area.

Kyren Williams (RB, LAR)

Although Blake Corum is eating into more of the rushing share this year, Kyren Williams still qualifies as a bell-cow back for the amount of work he gets with the Rams. Williams is seventh in snap share, seventh in carries, ninth in red-zone touches, and sixth in rushing yards. Travis Etienne Jr. had some big carries against the 49ers last week, and Williams should be able to run all over an injured defensive unit from San Francisco.

Possible Starts for Fantasy Football Lineups

Jauan Jennings (WR, SF)

UPDATE: Jauan Jennings has been ruled out for Thursday

Jauan Jennings was listed as a non-participant in the simulated practice report the team released on Monday, and he is looking very iffy to play on Thursday. Because of the other injuries on the team, Jennings will need to be started if he plays, but he has been up and down in his three games played. After five receptions for 89 yards and a touchdown in Week 2, he missed Week 3 and only caught two balls for 24 yards in Week 4.

Jake Tonges (TE, SF)

UPDATE: I would elevate Jake Tonges to a Must Start with all of the receivers now out for San Francisco. 

Since George Kittle went down with an injury, Jake Tonges has two games with a touchdown and three games with at least 68% of snaps played. Tonges is a touchdown-or-bust type of player who can be found on most waiver wires, but he can be a capable bye-week replacement since Brock Purdy clearly has a rapport with him.

Brock Purdy (QB, SF)

UPDATE: Brock Purdy has been ruled out for Thursday

I would tread carefully with Brock Purdy this week and only start him in two-QB leagues or in deep leagues where you have no other options. Purdy was clearly hindered by his toe injury against Jacksonville (two interceptions) and came out of the game stating it is sore again. The Rams have been pressuring the quarterback at a very high rate and have made mid-level quarterbacks like Daniel Jones and C.J. Stroud look quite bad so far.

Brock Purdy says his toe doesn’t feel nearly as bad as he did after Week 1. The curve ball this time is the short week. He also is wearing a cool hat pic.twitter.com/JZfLl2s2pG

— David Lombardi (@LombardiHimself) September 30, 2025

Blake Corum (RB, LAR)

Blake Corum is more of a consideration for 12- or 14-team leagues, but his usage over the last three weeks is very encouraging. Corum has played on 30% of snaps in two of the last three weeks. His touches have gone up each of the last four weeks, culminating in 11 touches in Week 4. If the Rams do get up by a touchdown or more in this game, I like Corum to spec a decent amount of the second half on the field.

Matthew Stafford (QB, LAR)

Matthew Stafford has at least 245 passing yards or two passing touchdowns in every game this season. Week 4 was his pièce de résistance of 2025 so far with 375 passing yards and three touchdowns against an overmatched Indianapolis secondary. Despite the injuries, the San Francisco defense has played quarterbacks tough this year, only allowing 13.2 fantasy points per game. But it has zero interceptions and is just 26th in sack rate. Stafford will have plenty of time to find his favorite receivers in this game.

Consider Sitting for Fantasy Football Lineups

Demarcus Robinson and Kendrick Bourne (WRs, SF)

UPDATE: I would elevate Demarcus Robinson to a Possible Start with all of the receivers now out for San Francisco. 

This recommendation comes with a huge caveat that's tied to Jauan Jennings and Ricky Pearsall. I would never expect the 49ers to sit both of those wide receivers this week, but if, for some reason, they do, Demarcus Robinson becomes very interesting. He returned from suspension and immediately played 39% of the snaps. Kendrick Bourne was also involved with 67% of snaps last week.

Brian Robinson Jr. and Isaac Guerendo (RBs, SF)

Christian McCaffrey has the third-highest running back snap share in 2025 at over 85%. That leaves less than 15% of the team's running back opportunities to share between Brian Robinson Jr. and Isaac Guerendo. In the last two games combined, Robinson and Guerendo have totaled seven touches.

Jordan Whittington and Tutu Atwell (WRs, LAR)

Don't let the one target, one catch, one 80-yard touchdown for Tutu Atwell fool you this week. It may look nice in the fantasy box score, but Atwell and Jordan Whittington are not involved enough in the passing game to make much of a fantasy difference outside a long busted play like Atwell saw in Week 4. Both Atwell and Whittington have target shares below 5% this season.

Tyler Higbee (TE, LAR)

Tyler Higbee has topped out at a 55% snap rate in three of four games and has 11 total targets through those four weeks. In two of those four weeks, Higbee has been completely shut out, so he is not consistent enough to be considered this week.

Kirksey’s Thursday Night Football Picks

Current Spread: LAR -6.5
Over/Under: 47.5

By the time the clock hit zero in their game against Jacksonville, the 49ers looked so beat up and just ready for the game to end. I worry that even if all of these questionable guys play, they won't be near full strength at all (UPDATE: They won't be). Add in the fact that they are on the road this week and McCaffrey is dealing with some huge inefficiencies, and I'm fully leaning Rams in this one.

The Rams have been able to lock running backs up this year, and only allow 7.9 fantasy points per game to the position, the best in the NFL. If San Francisco has a bunch of injuries and its best player can't find room to run, it's going to be a problem for it all night.

Give me the Rams in this one by a final score of 28-17.

The Pick: LAR -6.5, UNDER 47.5

2025 Overall Record:
Spread (3-1), Over/Under (3-1)

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