The European Club Association (ECA) has expressed its "deep concerns" regarding player welfare before the upcoming Africa Cup of Nations and is seeking urgent talks with world governing body Fifa.
The independent body highlighted the "worsening public health situation" following the emergence of the Omicron variant of coronavirus, which was first discovered in South Africa last month.
The developments may lead to a fresh dispute over releasing players for international duty next month.
The Nations Cup begins in Cameroon on 9 January and runs until 6 February, while there is another international window between 24 January and 2 February for some other confederations.
The ECA wants to work with world governing body Fifa to "ensure all necessary precautions are in place to protect players and club interests" as the health situation "continues to deteriorate in an alarming manner".
Countries have begin reintroducing travel bans, quarantine requirements and other restrictions because of concerns about the impact of the Omicron variant.
The United Kingdom has added 10 southern African countries to its travel red list.
The ECA is understood to be desperate to avoid a repeat of the problems during September's international window.
At that time Premier League clubs refused to release players for duty in red-list countries because at the time they would have been required to quarantine in a government-approved hotel for 10 days on their return to the UK.
Four England-based Argentina internationals did report for their country, but their presence led to the abandonment of the 2022 World Cup qualifier against Brazil on 5 September.
Brazilian health officials said the four players in question - Aston Villa's Emiliano Martinez and Emiliano Buendia and Tottenham's Giovani Lo Celso and Cristian Romero - had breached local rules on quarantine, with the UK then on Brazil's red list.
Meanwhile, the ECA has voiced its "unanimous" opposition to a biennial World Cup, a proposal that the Confederation of African Football has backed.
Fifa president Gianni Infantino is keen to hold the tournament, which is being expanded to 48 teams for the 2026 edition, every two years rather than in a four-year cycle.
Chaired by Paris Saint-Germain president Nasser Al-Khelaifi, the ECA says its position represents over 240 professional clubs in Europe, while European clubs provided almost 90% of the players who featured in the knockout stages of the 2018 World Cup in Russia.
It said the new international match calendars for men's and women's football must ensure the "right balance" between the club and international game, and take into account the voice of club football and the ECA in any decisions taken.