Defender Leah Williamson has been ruled out of England's Women's World Cup qualifiers this month because of "a significant" hamstring injury while her Arsenal team-mate Jordan Nobbs has been recalled to Sarina Wiegman's squad.
Williamson faced Tottenham on Saturday but later "experienced discomfort".
Gunners manager Jonas Eidevall said scans showed the injury may "possibly leave her out this whole year".
The 24-year-old has captained England in every game since Wiegman took over.
In addition to missing games for her country, she would be absent for up to seven games for Arsenal if she is ruled out until 2022.
Her Gunners team-mate Nobbs has been called up by the Dutch manager for the first time, having previously been ruled out because of her own injury problems.
England face Austria at the Stadium of Light in Sunderland on Saturday, 27 November before taking on Latvia at Doncaster Rovers' Keepmoat Stadium three days later.
The Lionesses are top of their group after four games, having scored 32 goals and conceded none so far.
Manchester City's Ellen White is poised to earn her 100th England cap with her next appearance for the Lionesses. She is also closing in on Kelly Smith's scoring record for England, needing just two more goals to equal the Arsenal great's tally of 46.
White has scored five goals so far in four games during the qualifying campaign.
'Put player's welfare first'
Like White, Williamson has been instrumental for the Lionesses since Wiegman took charge after Hege Riise's interim spell in charge.
The Arsenal defender, who also played under Riise for Team GB at the Tokyo Olympic Games in the summer, captained England for the first time in September in place of the injured Steph Houghton.
Gunners boss Eidevall said her hamstring injury is "of course an overloading issue".
"We need to work on so many different levels and put the player's welfare first ," he said.
"We shouldn't look at injuries as something we can't learn from. What could we have done differently? It could be scheduling, it could be co-operation with the national team and it could be how we load the players internally at the club."
England squad: Mary Earps, Hannah Hampton, Sandy MacIver, Millie Bright, Jess Carter, Niamh Charles, Rachel Daly, Alex Greenwood, Demi Stokes, Lotte Wubben-Moy, Jordan Nobbs, Jill Scott, Georgia Stanway, Keira Walsh, Katie Zelem, Bethany England, Lauren Hemp, Fran Kirby, Beth Mead, Nikita Parris, Alessia Russo, Ella Toone, Ellen White.