The "Atonement" star was expected to take on the lead of Cora, a newly-widowed woman tackling local superstition in Victorian England on the period piece, but she has since had to "unfortunately pull out" of the Apple TV+ project for "family reasons" related to coronavirus concerns, amid rising COVID-19 cases in the U.K. and another potential lockdown.
Knightley's representative adds to the Daily Mail, "There wasn't a comfortable scenario for Keira that could be put in place for an extended period of childcare required for the four-and-a-half-month production."
Knightley's withdrawal from the series has put the project on "hiatus." Costume designers, make-up artists and directors were reportedly shocked to be told the news earlier this week.
The Brit shares daughters Edie, five, and one-year-old Delilah with her husband, rocker James Righton.
A new actress for the role has yet to be announced. Kiera would have been likely to receive a six-figure salary for taking part in this drama, according to industry insiders.
Director Clio Barnard is taking charge of "The Essex Serpent" series, based on the critically-acclaimed 2016 book by Sarah Perry. Knightley was also set to be an executive producer of "The Essex Serpent".
Knigtley last starred in British comedy drama film "Misbehaviour", which was released in March of this year.