We're admittedly playing a bit of a guessing game when it comes to the 49ers injuries, but it appears Nick Mullens will start at quarterback, making him a fine Superflex option against a middling Philadelphia pass defense that ranks No. 23 in DVOA. The first nine starts of Mullens' career have quietly been historically good, and San Francisco's receivers are getting healthier (but no, he's not replacing Jimmy Garoppolo).
This week, the 49ers opened Deebo Samuel's practice window , but fantasy managers shouldn't plan on using him until Week 5 at the earliest, while Brandon Aiyuk should once again be among San Francisco's leaders in targets Sunday night against a beatable Eagles secondary. Aiyuk possesses the same wingspan as Calvin Johnson, benefits from seeing carries in Kyle Shanahan's system and looks like a strong dynasty league pick and a fine Week 4 start.
George Kittle looks ready to return to action, and he was targeted heavily by Mullens when they last played together in 2018, so he can immediately be treated like a top-five fantasy tight end in Week 4 with unmatched upside (at his position) moving forward if he's truly healthy.
It appears Jerick McKinnon is going to be given as many touches as his body can currently handle. McKinnon is a top-20 fantasy back this week, while Jeff Wilson Jr. remains a threat to score at the goal line and can be used as a flex option in deeper formats.
Zach Ertz should see all the targets with seemingly every Eagles receiver injured (including TE Dallas Goedert), also making Greg Ward Jr. a PPR sleeper. It's not going to be fully sustainable with so many SF injuries, but the 49ers have allowed the fewest fantasy points to running backs this season, so expectations for Miles Sanders should be tempered.
The 49ers defense can be started with confidence, as they are facing a winless Eagles team that has to travel across the country after just playing an overtime game that lasted five quarters, is decimated by injuries along their offensive line and has a struggling quarterback in Carson Wentz, who ranks nearly last in completion percentage. Wentz should be benched in fantasy leagues against an SF defense that's allowed a league-low 5.7 YPA and the fewest trips (four) to the red zone this season.
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.