The Blues take on the French champions at Stamford Bridge on February 22, before they travel across the channel to northern France for the second leg on March 16.
The French government do not allow unvaccinated people to enter the country.
Chelsea hoped that the second leg of their knockout clash could be played at a neutral venue so Thomas Tuchel could utilise his whole squad. UEFA issued new rules on Tuesday meaning a switch is not possible.
Tuchel's side have not disclosed the number of players or names of the unvaccinated, with the squad currently in Abu Dhabi gearing up for their Club World Cup match against Al-Hilal.
Following UEFA's rules, it is likely to provide Tuchel with selection problems ahead of the tie.
The Chelsea boss tested positive for Covid-19 on Saturday and was absent as his side defeated Plymouth Argyle 2-1 in the FA Cup fourth round.
Tuchel hasn't travelled with the squad to the United Arab Emirates, but has vowed to deliver a virtual team talk to his players.
Meanwhile, goalkeeper Edouard Mendy has linked up with his teammates following his Senegal Africa Cup of Nations triumph.
"At some point, everybody who is not vaccinated will face some consequences", Tuchel previously told the Mirror.
"If players are not allowed to travel to France, this can create problems for us in not being able to use key players.
"I'm not so sure about it. I simply don't know, I took my decision for myself. For us isolated as a club, isolated as a football team, there can be huge consequences.
"For example, if players are not allowed to travel to France, this can create problems for us in not being able to use key players.
"We are aware of it. It is a constant noise, a constant sound."
The Premier League revealed earlier this month that 80 per cent of its players had been double jabbed.