The 49ers come off their bye with Jimmy Garoppolo back at quarterback. He'll be playing through a calf injury, without George Kittle and in possible windy/rainy conditions Sunday night. While the 49ers would surely prefer to protect a less than 100% Jimmy G in poor weather, San Francisco may be forced to pass more than usual while up against DVOA's No. 1 run defense (compared to Indy's 29th ranked pass defense), so he's a fantasy option during a week with a whopping six byes.
Rookie Trey Lance remains sidelined with a sprained knee, although that might be moot with it becoming abundantly clear coach Kyle Shanahan plans on starting Jimmy G all season barring injury. Lance possesses approximately 10 times the fantasy upside as Garoppolo, but managers will simply have to wait for now.
Elijah Mitchell has fewer than 10 carries over the last month but enters Week 7 as a legitimate top-15 fantasy RB with so many byes, injuries and committees at the position throughout the league. There's no guarantee, but expectations are that Mitchell leads San Francisco's backfield, albeit against a Colts defense that's allowed the fourth-fewest fantasy points to running backs this season. Trey Sermon and Jeff Wilson Jr. both remain strong bench stashes.
Deebo Samuel enters ranked top-five in receiving yards and yards per route run this season while still leading the league in yards after the catch despite coming off a bye. A game that calls for extra passing yet in possibly poor weather conditions sure sounds like a perfect setup for Samuel, whose average depth of target has been a modest 8.6 yards this year. Especially with no Kittle and in a matchup against a tough run defense, Samuel should be considered a top-10 fantasy receiver in Week 7. Brandon Aiyuk continues to have too much upside to drop yet too much risk to trust in fantasy lineups right now.
The 49ers defense has disappointed this year but is coming off a strong performance in which they held an undefeated Cardinals team to 14+ fewer points than any other game this season. San Francisco's fantasy defense is a strong start this week at home coming off a bye and facing a quarterback who threw the most interceptions and took the most sacks last season despite missing four games.
Carson Wentz has admittedly played much better of late, getting 9.8 YPA with a 6:0 TD:INT ratio over the last three games. Still, given the matchup and weather conditions, he's more of a Superflex option this week. The Colts could get Quenton Nelson back, and Jonathan Taylor is a star, so he's an easy top-10 fantasy RB this week. But expectations should be tempered, as his workload can be maddening, and the 49ers have not allowed a 100-yard rusher an NFL-high 25 straight games. With T.Y. Hilton looking highly questionable to play, Michael Pittman should be treated as a top-25 fantasy receiver Sunday night.