McCaffrey exited Sunday's game at Cleveland due to an oblique injury, Nick Wagoner of ESPN.com reports.
In what has been a rough and tumble affair in rainy weather, McCaffrey is the second top skill-position player for the 49ers to depart after wide receiver Deebo Samuel (shoulder) was knocked out in the first half. If McCaffrey is unable to return, he'll leave Week 6 with 11 carries for 43 yards and three catches (on three targets) for nine yards and a touchdown. In McCaffrey's absence, Elijah Mitchell and Jordan Mason will man San Francisco's backfield.