McCaffrey was listed as questionable for Monday’s game after being limited in practice all week, but he will now miss his first game due to injury since joining the 49ers in Week 7 of the 2022 season.

On August 6, head coach Kyle Shanahan announced that McCaffrey was nursing a calf injury and that the team would be cautious about his health. This resulted in CMC sitting out of the 49ers’ preseason games and most of their training camps.

McCaffrey, however, spoke to the media on Friday, which is often a positive sign.

Jordan Mason and rookie Isaac Guerendo will now assume the running back duties as veteran Elijah Mitchell is out for the rest of the season and CMC is sidelined Monday night.

McCaffrey won the NFL rushing title with 1,459 yards and set a league record of 2,023 scrimmage yards and 21 scrimmage TDs. He was also named the AP’s NFL Offensive Player of the Year.

How long one of the league’s brightest prospects will be out remains to be seen.

For now, he’ll be watching in street clothes as the 49ers look to get off to a winning start tonight when San Francisco kicks off against New York at 8:15 p.m. Eastern Time.