The 49ers somehow scored the most points in the NFL in Week 1 yet were also arguably the most frustrating fantasy team. Trey Sermon was a surprise inactive after it appeared he locked up the RB2 role in camp, while Brandon Aiyuk shockingly saw zero targets. Jimmy Garoppolo even had a goal-line TD pass stolen (although 49ers fans aren't complaining seeing Trey Lance toss a touchdown on his first career pass), while Raheem Mostert lasted just two carries before suffering a season-ending injury.
Of course, there was a lot to like with the offense scoring 40+ points and getting 8.0 yards per play, although the team gets a tougher matchup this week in Philadelphia against an Eagles defense coming off one of Week 1's best performances. Jimmy G is only a Superflex option in this matchup with the threat of Lance stealing scores, while Aiyuk is safest on fantasy benches with so much uncertainty surrounding his situation. Players with his pedigree who put up his type of rookie numbers almost always turn into stars, so Aiyuk shouldn't be dropped in any fantasy leagues despite the frustrating start.
Sermon also needs to be held on fantasy benches, while rookie Elijah Mitchell appears to be the team's current lead back. It's a fluid (and maddeningly unpredictable) situation that's likely to change throughout the season (with Jeff Wilson Jr. eventually returning). But after JaMycal Hasty whiffed multiple times in pass protection last week, Mitchell should get another shot at leading SF's backfield in touches in Week 2. With 4.4 40 speed, Mitchell looks like a Mostert clone and suddenly has fantasy upside that's through the roof; there was good reason he went for 100% of free agent budgets in some leagues this week.
Deebo Samuel leads the NFL in target share after Week 1 and has already nearly matched his air yards total from last season. His fantasy value may never be higher, but Samuel is a must-start in all leagues right now. George Kittle also remains a weekly top-five fantasy TE and a staple in all lineups.
Good thing the 49ers defense has been facing Lance in practice, as Jalen Hurts' mobility is a problem. Hurts looked great in Week 1 while attempting much shorter throws under Philadelphia's new coaching staff, and he'll benefit from San Francisco losing top corner Jason Verrett for the season. A late onside kick recovery and lost fumble certainly both contributed, but Jared Goff scored the third-most fantasy points among all QBs against this defense in Week 1. Hurts is a must-start in all fantasy leagues.
The 49ers allowed a bunch of fantasy points to Detroit's running backs last week, but odd circumstances helped the Lions run nearly 90 plays, and there's hope Javon Kinlaw returns Sunday. Still, Miles Sanders is a strong fantasy start, while rookie Kenneth Gainwell is a sneaky flex option in PPR leagues. Dallas Goedert would get a boost should Zach Ertz (questionable, hamstring) sit, while DeVonta Smith is an exciting rookie well worth using in fantasy leagues, especially against a San Francisco secondary dealing with injuries.
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.
For Del Don's Week 2 Fantasy Preview: Figuring out the 49ers Backfield and other fantasy insight from around the league, visit here.