Kittle injured the groin in a light practice on Monday and has not been able to get back on the field for the first two major practices ahead of Sunday’s opener at Soldier Field.
Coach Kyle Shanahan had characterized the injury as day to day.
The Niners were cautious with Kittle during training camp after he missed three games last season with a calf injury. He got an extra day off here and there in an effort to keep him healthy going into the season.
Kittle hasn’t played a full season since 2018 because of foot, knee and hamstring injuries.
He had 71 receptions for 910 yards six touchdowns in 14 games last season. With Kittle unable to go, the Niners have Charlie Woerner, Ross Dwelley and Tyler Kroft as options on the active roster and Troy Fumagalli on the practice squad.
The Associated Press contributed to this report