England captain Leah Williamson is set to miss this summer's World Cup and the rest of the season with an anterior cruciate ligament injury.
Arsenal said: "Leah is set for an extended spell on the sidelines," adding that she will have surgery "in due course".
England's opening World Cup match with Haiti takes place on 22 July.
The 26-year-old, who captained England to their European Championship victory in 2022, is the latest injury setback for Sarina Wiegman's Lionesses.
ACL injuries typically see sports players sidelined for six to nine months.
England are already expecting to travel to the tournament in Australia and New Zealand without Beth Mead, who finished top scorer last summer, because of an ACL injury.
There are doubts over Chelsea forward Fran Kirby's availability, having been out of action since February.
Chelsea defender Millie Bright has also been on crutches with a knee injury sustained in March.
WSL defends pitch standards after Eidevall warning
Williamson was injured after just 15 minutes of Wednesday's WSL match at Leigh Sports Village after falling awkwardly while chasing possession and immediately signalling that she needed to be replaced.
A stretcher was initially brought on to the pitch, but a limping Williamson was able to walk off with support from a member of Arsenal's medical staff.
Arsenal manager Jonas Eidevall said afterwards: "You see the pitch, it is a pitch that has a lot more to [be desired]. I think it's going to continue here with the schedule we have and pitches like that, players are going to get injured."
He added that facilities need to improve to "keep players on the pitch".
On Friday a WSL spokesperson said pitches at WSL stadiums are monitored throughout the season with "steps taken" to support clubs where necessary.
Arsenal have already been impacted by serious injuries to key players this season including captain Kim Little, Ballon d'Or runner-up Mead and last season's top scorer Vivianne Miedema.
Analysis - England's World Cup hopes dented
Emma Sanders, BBC Sport
It is the worst possible news for Sarina Wiegman with three months to go until the World Cup.
Williamson's importance to England cannot be understated. She is the captain, part of a formidable centre-back partnership with Millie Bright and a calming influence on her team-mates.
She started and captained every game as England won Euro 2022 last summer and played in 22 of the Lionesses' incredible 30-match unbeaten run.
With Arsenal team-mate Beth Mead already ruled out with an ACL injury, England are now almost certainly without last summer's top scorer and their captain, while Chelsea's Fran Kirby and Bright are currently on the injury list, adding to concerns.
'With you every step of the way' - support for Williamson
Williamson received plenty of support on social media with the England national team responding on Instagram:external-link "You'll come back stronger than ever."
Team-mate Mead said on Twitterexternal-link: "We are with you every step of the way, even if I have to be quiet some days in rehab.
"We got you girl, all the love and strength in the world."
Meanwhile Fifpro, a global union for professional footballers, said on Twitter:external-link "As news of Leah Williamson's World-Cup-ending ACL injury breaks, the words of her England team-mate Beth Mead have never rung truer.
"More. Research. Needed."
