The team announced Friday that Shepard would be unable to suit up in Week 2.
Shepard suffered the concussion in New York's Week 1 loss to the Dallas Cowboys, which further limited a wide receiver corps that is without Golden Tate until Week 5 due to a performance-enhancing drugs suspension and Corey Coleman for the year because of a torn ACL.
The Oklahoma product also suffered a broken thumb during the offseason and missed time in training camp and the preseason.
He appeared in all 16 games last year and finished with 66 catches for a career-best 872 yards and four touchdowns. Shepard was largely expected to serve as a top option in the passing attack with Odell Beckham Jr. no longer on the roster. He did have six receptions on seven targets against the Cowboys.
While the Giants have dealt with attrition at the wide receiver position this year, they can still turn to receivers Bennie Fowler and Russell Shepard. They also have tight end Evan Engram as a dangerous pass-catcher to help quarterback Eli Manning.