The 49ers don't have to travel far and are coming off a Bye, while the Rams are coming off a big road win Monday night. So, the setup helps San Francisco, but that's likely not enough against one of the league's best defenses and with Trent Williams joining the laundry list of 49ers on the Reserve/COVID-19 list. The availability of Raheem Mostert, Brandon Aiyuk and Deebo Samuel remains unclear, and those reinforcements would certainly help Nick Mullens versus an LA defense that has allowed the fewest passing touchdowns (11) this season and an NFL-low 6.1 YPA, with the next best defense ceding 6.6. Mullens is only a desperate option in Superflex leagues given the matchup and likely protection issues.
Mostert, Samuel and Aiyuk can be started as flex options if active, while Jordan Reed is a deep sleeper at a thin tight end position assuming he suits up, as Kyle Shanahan's schemes can keep the team's offense afloat (but it should be noted LAR has given up the fewest fantasy points to outside receivers this year). If Mostert sits again, the 49ers backfield is one to avoid against a dominant Rams defense that's allowed the fewest yards per play this season facing an undermanned San Francisco squad absolutely devastated by injuries.
Jared Goff leads the NFL in adjusted completion percentage (85.8) this season in a clean pocket, and the 49ers have struggled mightily getting to the quarterback lately. SF has a tough run defense not unlike LA's opponent last week (Tampa Bay Buccaneers), so it's entirely possible the Rams surprise and go pass-heavy yet again Sunday, making Goff, Cooper Kupp and Robert Woods strong fantasy starts and Josh Reynolds a sleeper. The Rams are arguably the top fantasy defense this week, although it's best to avoid the team's backfield which has become a three-headed committee and is facing a 49ers defense allowing just 3.9 YPC this year.
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.