Rookie Ahkello Witherspoon and Pita Taumoepenu are active for the first time this season as the 49ers prepare to play the Colts.
Witherspoon, a third-round pick in April, likely will be used on special teams because fellow rookie Adrian Colbert is out with a hamstring. He also will be the top backup at outside cornerback behind starters Rashard Robinson and Dontae Johnson.
Taumoepenu is active because Dekoda Watson is out with a groin injury. He will be a backup at both strong-side linebacker and defensive end.
Meanwhile, receiver Marquise Goodwin will start despite suffering a concussion Sunday, his fourth in the last 14 months.