Here is the Pickwatch BetSmart Preview for the San Francisco 49ers vs. Los Angeles Rams in Week 5 of the 2025 NFL Season.

San Francisco 49ers vs. Los Angeles Rams Game Info

Date: Thursday, October 2, 2025
Time: 8:15 PM ET
Location: SoFi Stadium — Inglewood, California
TV: Amazon Prime Video (national TNF broadcast)

49ers vs. Rams Betting Odds

Point Spread
- 49ers -8.5
- Rams +8.5
Moneyline
- 49ers +340
- Rams -400
Total
- Over 46.5
- Under 46.5

*Odds via FanDuel

Season Betting Records

Moneyline
- 49ers: 3-1
- Rams: 3-1
Against the Spread
- 49ers: 2-2
- Rams: 3-1
Totals (Over-Under)
- 49ers: 2-2
- Rams: 2-2

San Francisco 49ers (3–1) @ Los Angeles Rams (3–1) Preview

The 49ers are entering this matchup already shorthanded — Brock Purdy is ruled out due to turf toe, and wide receivers Jauan Jennings and Ricky Pearsall are also out. Mac Jones will start in his place, though he has limited tape this season.

San Francisco will lean heavily on Christian McCaffrey to carry much of the offensive load — he’s leading the team both in rushing and receptions — and the 49ers’ performance will depend on how well their run game can offset their passing deficiencies. Their defense also faces challenges: without Nick Bosa (season-ending ACL), San Francisco struggles to generate consistent pressure without overextending.

The Rams, meanwhile, come in as strong home favorites. Matthew Stafford and the passing attack — featuring Puka Nacua and Davante Adams — have been clicking, and LA’s defense has shown flashes of dominance against dynamic backs. But even the Rams are dealing with injury concerns: tight end Tyler Higbee and tackle Rob Havenstein are listed as doubtful.

Betting markets have shifted toward a double-digit Rams spread, reflecting confidence in their depth and fewer offensive injuries. Some analysts also lean Under 46.5, expecting a hard-hitting battle rather than a shootout.

49ers/Rams Head-to-Head (H2H) Stats and Analysis

Their most recent matchup was last season, which the Rams won 12-6. The 49ers lead the all-time series, 78-71-3.

Rams 12, 49ers 6 — December 12, 2024
Rams 27, 49ers 24 — September 22, 2024
Rams 21, 49ers 20 — January 7, 2024
49ers 30, Rams 23 — September 17, 2023
49ers 31, Rams 14 — October 30, 2022

BetSmart Betting Rundown

The Pickwatch BetSmart subscription package provides valuable sports betting tools that will help you wager wisely on the 49ers vs. Rams game and start building bankroll. Sign up for a 14-Day Free Trial today and get instant access to our proprietary tools and data.

Arbitrage

Our Arbitrage Betting Tool has identified 3 arbitrage betting opportunities for guaranteed profit.

Middles

Our Middle Betting Tool has identified 26 different middle betting opportunities, some of which are among the Most Profitable Markets so far this season.

Positive EV

Our Positive EV Betting Tool has identified 12 different positive expected value wagers, and provided data on the expected value percentrage, suggested Kelly Stake, and how often the bet has hit in the last 5, 10 and 15 games.

Player Props

Our Prop Finder Tool has identified over 100 different player prop bets, and provided data on how often each player has hit the specific prop in the last 5, 10 and 15 games. Here's some props you can get data on:

Matthew Stafford Total Passing Yards: Over/Under 239.5
Christian McCaffrey Total Rushing Yards: Over/Under 59.5
Puka Nacua Total Receiving Yards: Over/Under 95.5

49ers vs. Rams: Expert Picks

Visit our Expert Picks page to view picks and data from over 200 experts to see where the consensus is on the 49ers vs. Rams moneyline, point spread and total points.