Jimmy Garoppolo struggled badly while trying to play through a high-ankle sprain last week, and he'll look to bounce back against a Rams team that's allowed the second-fewest yards per play this season and has a pass defense that ranks #2 in DVOA. San Francisco enters with a distinct disadvantage up front, so there's a real chance Garoppolo doesn't finish this game yet again, making him a risky fantasy start.
Raheem Mostert looked like the best player on the field last week during his return from a sprained knee, and he should dominate backfield work Sunday against a Rams defense that's much easier to run rather than throw against (LAR ranks #24 in run defense DVOA). Mostert is a borderline RB1 and a must-start in fantasy leagues for as long as his health cooperates this season.
Deebo Samuel returned to a full workload of snaps last week, but he and Brandon Aiyuk get a Rams defense Sunday night that's yielded the fewest fantasy points to wide receivers this season, so they belong on fantasy benches, especially given the sudden uncertainty with QB play in SF right now (and competition for targets with everyone healthy). As usual, George Kittle has an argument as this week's TE1, although Nick Mullens is the SF QB who targets him most.
The Rams have deployed a conservative offense this season (extremely run heavy in neutral situations and with Jared Goff having the lowest average intended air yards in the NFL) but are tied for fifth in yards per play anyway, and Goff has 10 touchdowns over the last four games. He also leads the NFL with 9.0 YPA and is a strong fantasy start (along with Robert Woods and Cooper Kupp) against a San Francisco defense that's missing seemingly every member of its secondary to injuries.
Darrell Henderson isn't without risk in an unpredictable backfield but also carries major fantasy upside and is well worth the gamble with the league full of question marks at the running back position right now. Tyler Higbee ran just 15 routes last week and leads all tight ends in pass block snaps this season, so he should be closer to a fantasy drop than your starting lineup.
Dalton Del Don has been with Yahoo Sports since 2013, covering fantasy football, baseball and basketball. He appears on multiple podcasts each week and currently resides in the Bay Area, where he is an avid fan of the Golden State Warriors and 49ers.