Indianapolis Colts left guard Quenton Nelson was activated off injured reserve on Saturday and is expected to play against San Francisco on Sunday night.
The Colts (2-4) also placed safety Julian Blackmon on injured reserve and ruled out wide receiver T.Y. Hilton for the road game against the 49ers (2-3).
Nelson, a three-time All-Pro, has missed the past three games with a high-ankle sprain.
Prior to the injury, Nelson started 51 consecutive games to begin his career after being taken by the Colts with the sixth overall pick of the 2018 NFL Draft. The 25-year-old has made the Pro Bowl in each season of his career so far.
Blackmon, 23, sustained a torn Achilles in practice on Wednesday.
He has 34 tackles (two for loss), one pass defended and one forced fumble in six starts in 2021.
The 2020 third-round pick stepped into a starting role when Malik Hooker injured his Achilles last season.
Hilton, 31, was placed on IR in early September after neck surgery. He made his season debut last Sunday and had four catches for 80 yards before sustaining a quadriceps injury in a 31-3 victory over the Houston Texans.
Hilton has 612 catches for 9,440 yards and 50 touchdowns in 134 career games with the Colts. He made the Pro Bowl four straight years from 2014-17.
Also on Saturday, the Colts elevated wide receiver Keke Coutee and safety Josh Jones to the active roster from the practice squad.