Chelsea and England midfielder Fran Kirby will miss the World Cup because of a knee problem that requires surgery.
The 29-year-old’s club said on Tuesday that she was expected to be out for a “significant period”.
A “gutted” Kirby later confirmed on social media that her World Cup ambitions were over.
It is the latest injury setback for England boss Sarina Wiegman, who has also lost captain Leah Williamson.
“Unfortunately after a few months of rehab the decision has been made that I will require surgery on my knee,” Kirby said on Twitter.
“I have been trying my best to not have to undergo this but unfortunately my progress has been limited.”
She added: “I’m absolutely gutted to announce that this means my season is over and I will not be able to make the World Cup.
“I’m going to be doing everything possible to be ready for the start of next season.”
Kirby sustained the injury in the League Cup semi-final against West Ham in February.
Arsenal defender Williamson’s World Cup dream was ended by an anterior cruciate ligament injury suffered in April.
The European champions also expect to be without Arsenal forward Beth Mead, who finished top scorer last summer, because of an ACL injury, while Chelsea defender Millie Bright is continuing to recover from a knee injury she sustained in March.
The World Cup begins on 20 July.
‘Latest England blow arguably the biggest’ – analysis
BBC Sport’s Emma Sanders
This latest injury blow to one of England’s key players is arguably the most significant. Kirby is one of the country’s most gifted footballers and has often been described by team-mates and coaches as a player who can single-handedly win matches.
She started every match at Euro 2022, providing a creative spark and intricate attacking build-up play which proved crucial en route to victory.
Her England understudy Ella Toone will be a strong replacement at the World Cup but Kirby’s qualities will no doubt be a major loss.
It is also a huge blow for Chelsea as they continue their quest to win a fourth successive Women’s Super League title and the FA Cup. When fit, Kirby has built a formidable partnership with superstar forward Sam Kerr.
Having been plagued by injury and illness throughout her career, it is a sad ending to Kirby’s season and the World Cup this summer will be worse for her absence.