Aston Villa have allowed Emi Martinez and Emi Buendia to join the Argentina squad for World Cup qualifiers in defiance of a collective decision by English Premier League clubs not to release players to red-list countries.
English clubs had announced they would not permit players to travel to countries on the UK Government's COVID-19 list, prompting FIFA president Gianni Infantino to write to Prime Minster Boris Johnson to request exemptions.
However, Villa have confirmed goalkeeper Martinez and midfielder Buendia have travelled to South America.
Tottenham boss Nuno Espirito Santo on Sunday was coy on whether he would give the green light to his South American players, saying the club was trying to "anticipate the damage" caused by the move.
Villa's Martinez and Buendia have agreed to only play in Argentina's first two Cup qualifiers against Venezuela and Brazil and skip the game against Bolivia.
They still face missing a Premier League match against Chelsea while isolating for 10 days in a hotel room chosen by the government with no apparent ability to exercise significantly outside.
"Aston Villa can confirm Emi Martinez and Emi Buendia have travelled to join up with the Argentina squad with the permission of the club in accordance with FIFA's international match call-up rules," a statement said.
"These arrangements mean that Martinez and Buendia will only miss our Premier League match with Chelsea before being available for the visit of Everton to Villa Park on 18th September in order to comply with the UK's COVID quarantine regulations.
"There are no easy solutions as the COVID-19 pandemic continues to adversely impact professional sport.
"After careful consideration, we think this plan respects the long established call-up rules and balances the importance which top players place on representing their countries in important matches with the best interests of Aston Villa."
In addition to the issue of players missing fixtures due to quarantine, there is also concern that they could lose match fitness because of their inactivity.
Spurs manager Santo was more vague about whether his players would be allowed to go.
Tottenham's Cristian Romero and Giovani Lo Celso are in the Argentina squad while Spurs teammate Davinson Sanchez is due to link up with Colombia.
"We have to obey the government law," Nuno said.
"We will try to do so, but at the same time, we don't have any kind of help from FIFA, the government or the Premier League in support in this situation."
"We know what it means for all of the players to play for their national teams.
"It's something they're very proud of, so what we are trying to do is anticipate the situations.
"We are trying to take care of that situation. Trying to anticipate the damage. Us as a club, we are working on that."
Australian Associated Press