Niners GM John Lynch told KNBR-AM radio on Friday morning that McKinnon would be out of action until Week 1.
The 49ers face McKinnon's former team, the Minnesota Vikings, to open the 2018 campaign.
McKinnon was injured in practice Sunday. The team initially feared a knee injury, but an MRI revealed a minor calf strain that should clear up before the regular season.
McKinnon’s injury paired with backup running back Matt Breida’s shoulder injury prompted Lynch to go out and sign free agent Alfred Morris on Monday.
McKinnon, 26, underwhelmed in his preseason debut against the Cowboys last week with three carries and -4 yards. However, he’s expected to be a feature piece in the backfield with Jimmy Garoppolo when healthy.
"The good news is it's not going to be long-term, the bad news is it's going to take him up to Week 1, our opener, so his opportunity to get more in rhythm in our system, that kind of goes out the door," Lynch said. "But he's played a lot of football, and we play a lot of football in the offseason, OTAs and all that, so we're going to have to trust that he’s going to be ready."
Holding out McKinnon until the start of the season was the expected move for the 49ers. San Francisco gave McKinnon a four-year $30 million contract to be a dual-threat back in Shanahan's RB-friendly system. Even if it hurts his early-season production to miss reps in a new offensive system, the 49ers won't risk re-injury during the preseason.
With McKinnon and Matt Breida injured there are plenty of reps for youngsters Raheem Mostert and Joe Williams. Newly signed veteran Alfred Morris should also get additional snaps as he tries to win a roster spot.
