The decision of the Premier League clubs was clear: No players will be released to play for countries on England's "red list."
The announcement on Tuesday by the world's richest league highlighted the escalating backlash FIFA is facing over its decision to overlook coronavirus-related quarantine requirements and concerns of clubs and leagues to squeeze in more World Cup qualifiers in September and October.
The Spanish league also said it would support any of its clubs that did not want to release players for international duty with South American nations.
Unlike for other international fixtures during the pandemic, FIFA is no longer allowing exemptions for players to opt out of the trips if they are forced to quarantine on their return to countries to resume club duties.
With World Cup qualifiers also in Africa, Asia, the CONCACAF region and Europe, the clubs are on a potential collision course with FIFA.
They face FIFA sanctions if they refuse to release players but Liverpool have already told Egypt that Mohamed Salah won't be released for next week's games because he would face a mandatory 10-day hotel quarantine on returning to England.
Premier League clubs backed Liverpool's position, forming a unified front on Tuesday to "reluctantly but unanimously" block almost 60 players from 19 clubs going to 26 countries on England's red list that features all 10 South American countries.
The Spanish league - which has had 25 players from 13 clubs named in squads by South American nations - hit out at FIFA's "unilateral decision" to grant two additional days for CONMEBOL countries to play games in coming week so three qualifiers can be played in each window, rather than the usual two.
CONMEBOL is trying to complete most of qualifying in time for the 2022 World Cup draw in April and was granted approval for the triple-headers by the FIFA Bureau headed by Gianni Infantino earlier this month.
Concerns about FIFA's actions are being led by the European Club Association, which is headed by Paris Saint-Germain's Qatari president Nasser Al-Khelaifi.
"ECA has firmly expressed its objection to FIFA's decision and has urged FIFA to review its position," the organisation wrote to its member clubs last week.
The World Leagues Forum proposed to FIFA that South America's games could instead by played in a bubble.
It also proposed using the four blank international matchdays between May 30-June 14, 2022 to complete qualifying.
FIFA organises the World Cup, which generates most of the governing body's revenue of $6 billion in the four-year cycle, and regulates the game globally and oversees the international calendar.
FIFA declined comment beyond its August 6 statement announcing the additional South American qualifier in both September and October.