Tottenham and Aston Villa stars Cristian Romero, Giovani Lo Celso, Emiliano Martinez and Emiliano Buendia face missing Premier League games next month after being included in Argentina's squad for their World Cup qualifiers.
Argentina is currently on the UK's 'red travel list,' meaning the four Premier League players will be forced to isolate for 10 days on their return from South America.
Lionel Scaloni's men face World Cup qualifying matches against Venezuela, Brazil and Bolivia on September 3, 5 and 10.
The news will come as a blow for Spurs and Villa as it means they will all certainly at least miss one Premier League match and likely be unavailable for another one on the following weekend.
Lo Celso and Romero will either be travelling back or in quarantine on September 11 when Spurs take on Crystal Palace and are also expected to miss their London derby showdown against Chelsea on September 19.
Meanwhile, Martinez and Buendia, who have played in both of Villa's opening two matches this season, won't be able to face Chelsea or Everton as they will still be in isolation.
Argentina's decision to call-up four players from the Premier League comes just hours after a new club vs country row erupted on Monday, with Liverpool blocking Mohamed Salah, Roberto Firmino, Fabinho and Alisson from representing their international teams in a bid to avoid them being forced into a 10-day quarantine in a hotel.
Salah was called up to the Egypt squad for their World Cup qualifiers against Gabon and Angola while the other three players were set to be picked for Brazil's three fixtures.
Both countries have 'red list' status, so they would all have to isolate for 10 days, but Liverpool have taken a firm stance by refusing to let them join up with their international teams.
As things stand, Tottenham and Villa will not take a similar course of action.
Liverpool have since said they are prepared to release Salah for the Gabon game, because the country is on the UK's amber list - which does not have isolation rules for those who are fully vaccinated.
But the game with Angola is set to be played in Egypt's capital of Cairo. As Egypt is on the red list, Salah would need to quarantine after taking part in the match.
In a statement, Egypt said they have asked FIFA for a travel exemption, meaning Salah would be able to play for his country and not face quarantine when he returned to the UK.
Sportsmail reported that Premier League chiefs were lobbying Government for quarantine exemptions to avoid their star players being forced to isolate in hotels and face missing key Premier League and Champions League matches.
It comes after The Mail on Sunday revealed last week that FIFA have scrapped their temporary rule that allowed clubs to refuse to release players for international duty who faced more than five days quarantine.