All-Pro running back Christian McCaffrey is dealing with a calf injury, which results in him being listed as questionable ahead of the San Francisco 49ers' regular-season opener.
If you're thinking this applies to the Niners' 2025 Week 1 NFC West showdown against the Seattle Seahawks, you'd be correct.
Also, if you're reminiscing about San Francisco's season opener against the New York Jets a year ago at this time, you'd be correct, too. And, in that particular showdown, McCaffrey ended up being inactive with what turned out to be achilles tendinitis stemming from calf issues, which ultimately led to him missing the first eight games of the year.
Despite the 49ers' efforts to closely monitor and protect the 2023 Offensive Player of the Year to save his workload for both the regular season and (hopefully) playoffs, McCaffrey is again dealing with a calf issue, and that injury forced him into being a limited participant during the week's practices leading up to Sunday's NFC West bout in Seattle.
And that may spell trouble for the Niners, both in the short- and long-term pictures.
Christian McCaffrey's injury status is a cause for concern for 49ers
Here's the full Week 1 injury report for San Francisco:
Doubtful
RB Jordan James (finger)
WR Jordan Watkins (ankle)
Questionable
RB Christian McCaffrey (calf)
Again, the 49ers have been careful with McCaffrey throughout training camp and the preseason, so limited participation isn't necessarily a massive red flag, as NFL Network's Tom Pelissero reported.
.@TomPelissero does not get the sense that there are "alarm bells going off" about Christian McCaffrey. pic.twitter.com/wF5iJFXozW
— NFL Network (@nflnetwork) September 5, 2025
That said, the Niners had to have a key contingency plan in place if McCaffrey ends up missing a substantial amount of time, which helps explain the recent trade pickup of former Washington Commanders tailback Brian Robinson Jr.
Should McCaffrey wind up inactive for Week 1, Robinson's presence suddenly becomes vital and not just for the season opener. Potentially beyond, too, depending on the severity of CMC's injury.
Fortunately, though, San Francisco has a relatively clean slate of injuries before Sunday's contest.
The Niners' full list of inactives will be declared 90 minutes prior to kickoff, which will be at 4:05 p.m. on Sunday, Sept. 7.