Premier League clubs have asked their South American stars to withdraw from international duty early so they can be available to play when the season resumes.
On top of the uncertainty over which players are eligible for a quarantine exemption upon their return from international games, the World Cup qualifying schedule in South America has left clubs with another big concern.
Argentina, Brazil and Uruguay all play a week on Friday, with the Premier League restarting the next day.
Aston Villa goalkeeper Emi Martinez and Tottenham duo Cristian Romero and Giovani Lo Celso will meet up with the Argentina squad, while eight Premier League players including Thiago Silva, Emerson Royal, Alisson, Ederson, Fred, Fabinho, Gabriel Jesus and Raphinha have been named in the Brazil squad, while Manchester United striker Edinson Cavani will feature for Uruguay.