Also out are quarterback Jimmy Garoppolo, running backs Raheem Mostert and Tevin Coleman, defensive end Dee Ford, and linebacker Dre Greenlaw.
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Kittle suffered an MCL sprain and bone bruise during the 49ers' Week 1 loss to the Arizona Cardinals and was inactive this past weekend against the New York Jets. He practiced on Wednesday and Thursday, and until Friday, was a possibility to return for Week 3.
Shanahan said he spoke with Kittle before Friday's practice to determine where he is in his recovery. That led to ruling him out against the Giants.
"I thought it was a lot safer to leave him out," Shanahan explained to reporters. "That didn't need to wait another day because of how he sounds today."
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