The 22-year-old has been sidelined for a two-month period after suffering a knee injury against AC Milan in the UEFA Champions League a fortnight ago.
That effectively rules him out of England's trip to Qatar, with the World Cup kicking off barely in a month's time.
James, who recently extended his Chelsea contract until the summer of 2028, was expected to be England manager Gareth Southgate's first choice right back in Qatar.
Despite the prognosis of his setback, James still habours faint hopes of playing a role for his country at the Mundiale.
"It's obviously devastating and you know the World Cup is only a month away," James said on his YouTube channel. "As a kid, growing up, I always wanted to go and this is my first opportunity.
"I'll do everything I can to try to be there, but I'm obviously devastated. Just [the] injury came at the wrong time. But every day, we need to be grateful and thankful.
"I'll keep you updated with what's happening on a day-to-day basis, and I'll touch base soon."
James has so far featured 15 times for England.
The Three Lions are in the same group with Iran, Wales and USA at the World Cup group stage.