The Aragon government said the "drastic" measure is to be implemented after seven workers and 90 animals at a breeding farm tested positive.
Authorities in northern Spain have said that over 90,000 mink must be culled at a farm after around 90 animals tested positive for the coronavirus.
The Aragon regional government said it had to take the "drastic" measure that concerns 92,700 mink in accordance with national animal health laws.
The farm in Teruel province's La Puebla de Valverde has been kept in isolation since May 22 after seven workers tested positive.
The region's chief of agriculture and environment, Joaquin Olona, said there is no evidence of whether the virus was transmitted from the workers to the animals or the other way around.
"We are absolutely certain that the virus is present in these animals and community transmission between animals is taking place," Olona said, according to Spanish private news agency Europa Press. He added the goal of the culling was to avoid "risks to public health."
While previous studies have found that COVID-19 is contagious among some animals, like cats and dogs, far less is known about the possibility of animal-to-human transmission and researchers are looking into the subject.
Mink are semiaquatic, carnivorous mammals bred for their furs.
The Netherlands, one of the world's top exporters of mink fur, has already culled hundreds of thousands of mink since June 6.
As many as 24 mink farms have reported infections, according to a statement from the ministry for agriculture released earlier this week. Several employees at these farms have also tested positive.
So far, all the animals at 23 previous farms have been slaughtered.
The Dutch government has tightened the hygiene protocol for mink farms with a nationwide transport ban and a visitor ban in stables among the measures. Mandatory testing was also implemented.
It is also working on a scheme to allow farms to voluntarily shut their businesses ahead of the 2024 deadline when mink farming will be prohibited in the country.