Influential midfielder Sherry McCue is out for two months.
Villa Ladies star McCue injured her ankle in an England U19s international against Denmark at Burton's St George's on Tuesday.
Boss Joe Hunt said: "It's a big blow because Sherry is a special player for us.
"She has everything you want in midfield - vision, bite, tenacity, energy and leadership.
"She will be missed but at least we have other talented players to draw upon, the likes of Maddy, Katie, Abbeyleigh and Tash."
It was the only frustration from a momentous day for Villa, as six players represented the Three Lions in the friendly clash at new centre for national football.
McCue captained the side and was joined in the starting line-up by Mel Lawley, Maddy Cusack, Abbeyleigh Stringer and Aoife Mannion. Goalkeeper Megan Walsh came on as a substitute.
Villa are due to play Copsewood Ladies in the County Cup quarter-final on Sunday although boss Hunt is not confident the game will be on because of snow on the Boldmere St Michael's pitch.
Next week, Villa travel to Coventry City Ladies on Thursday in the League Cup quarter-final before an away tie with Ipswich Ladies in the third round of the FA Cup.