European Club Association (ECA) members are set to prevent their players from going to 'red-list' countries during September's international break unless quarantine exemptions can be made, with the Premier League currently in talks with the Department for Digital, Culture, Media and Sport (DCMS).
Argentina, Brazil and Egypt are among the nations currently on the UK Government's "red" list regarding travel to England, meaning a 10-day period of hotel isolation would be required before players can return to their clubs.
That would mean Mohamed Salah is unable to play Egypt's World Cup Qualifier in Cairo against Angola on September 2 - and the Egyptian FA says Liverpool have already informed them Salah will not be available - although the forward would be free to travel to play away in Gabon three days later.
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Unless quarantine issues can be resolved, a host of other Premier League players may be unavailable for international matches next month, so too PSG stars Lionel Messi and Neymar.
Brazil host Argentina in a World Cup Qualifier at the Maracana on September 5, and the ECA's current reluctance could rule out several players from that match and a host of other games in South America.
Eight Premier League players were named in the upcoming Brazil squad, with Liverpool trio Alisson Becker, Fabinho and Roberto Firmino joined by Ederson and Gabriel Jesus (both Manchester City), Thiago Silva (Chelsea), Fred (Manchester United), Richarlison (Everton), Raphinha (Leeds United).
Aston Villa and Argentina goalkeeper Emiliano Martinez, who started in the 1-0 Copa America final win over Brazil last month, would likewise be prevented from playing his nation's qualifiers.
Paris Saint-Germain are also ECA members, meaning Messi, Neymar, as well as Marquinhos and Angel Di Maria could also miss out with Argentina and Brazil among the nations on France's "red" list - the French government also operate a traffic-light system for travel.
Despite talks between the Premier League and DCMS it is understood that no agreement has been reached over exemptions for players.
Sky Sports News understands the Premier League and the FA, as well as other ECA members, are hoping to find a solution, with clubs willing to release players if quarantine rules are lifted while FIFA are optimistic an agreement similar to the one implemented during the Euros can be reached as it affects far fewer players - just under 100 in England.
Earlier this year, FIFA announced that the exemption allowing clubs not to release players for international duty would end, meaning Premier League clubs could face sanctions if they stop players joining up with their national sides.
The government denied exemptions to the British and Irish Lions players upon their return from South Africa earlier this month.
It is not yet known whether Barcelona, Juventus and Real Madrid, who did not retain their ECA membership following the European Super League fallout, will allow their players to travel.
Sky Sports News have contacted the ECA for comment.