In addition to the likely absence of quarterback Jimmy Garoppolo, San Francisco will be without its two top running backs in Raheem Mostert and Tevin Coleman.
Mostert isn't even with the team right now. A knee injury was going to keep him from playing, but he was already slated to leave his teammates and travel to Cleveland for the birth of his second son.
Neeko Rafe Mostert was born on Thursday.
Filling in for Mostert and Coleman will be Jerick McKinnon and Jeff Wilson, Jr. The team is likely to promote JaMycal Hasty from the practice squad, too.
ESPN's Nick Wagoner predicts a big game for McKinnon, who had 77 yards and a score on three carries against the New York Jets during Week 2.
"49ers running back Jerick McKinnon will have his first 100-plus-yard rushing game since 2014 and just the third in his career," wrote Wagoner. "With Raheem Mostert and Tevin Coleman out because of knee sprains, McKinnon will have an expanded role this week, and he gets it against a Giants defense that has been shoddy against the run over the first two weeks and hasn't seen a rushing attack as dangerous as the Niners' unit yet. McKinnon will take advantage and reach the end zone for the third time in as many weeks."
ESPN notes that it's been over 1,000 days since McKinnon had 15 carries in a game. The running back has recorded 101 rushing yards and a rushing touchdown on just six carries this season while adding three catches for 20 yards and a receiving score. He spent the past two seasons on injured reserve after suffering an ACL injury in 2018.
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