UEFA has warned Chelsea that they would have to leave unvaccinated players behind when they travel to face Lille in the Champions League last 16 next month.
The Blues host the Ligue 1 side at Stamford Bridge on February 22.
The return tie is scheduled to be played in northern France on March 16.
However, France is tightening its COVID-19 rules, insisting that all professional athletes competing in the country are vaccinated against the virus.
UEFA has now said “in principle”, it expects clubs to comply with local laws around COVID.
The French Ministry’s position is also expected to impact Real Madrid, who travels to take on Paris Saint-Germain on February 15 for the first leg of their knockout tie.
UEFA says it is still in discussion with stakeholders over its plans for the knockout stages of the European competitions and that more guidance will be provided.