The midfield duo have been training with the Under-23s side in London and will miss all three of the senior's team games in the United States.
“Yes, it has to [come into your thinking],” Tuchel told reporters ahead of the match at Allegiant Stadium. “I knew some players who I would also take without vaccination. I have to say," he added with a smile.
“But yes, it is a part of daily life at the moment.”
On Friday, Kante and Loftus-Cheek took part in the academy's match against London minnows Boreham Wood instead of facing Club America.
In Kante's case, Tuchel believes it will not prove a big issue. But, for Loftus-Cheek, he can see how a returning Conor Gallagher may use pre-season to take his place in the squad.
Tuchel is frustrated not to have his whole squad but is powerless to force his players to get vaccinated.
“We cannot force,” he added. “It is at the moment a very normal decision to get vaccinated. Both players took the decision not to. We need to follow the rules. They cannot join us. They know about the consequences.
“We don’t like it. Of course not. We would love to have them here and it is not an ideal solution. Far from ideal. But, once the situation is like this you need to come up with a solution. So they have their coaches there.
“They have coaches from us there who take care. They train with the Under-23s. Then they go with the Under-19s to not completely not be in a group. But it will not compensate. It will not be the same.
“For N’Golo it is maybe not even the worst thing to do. So we can give him a very individual load. Very, very individualised load for him. So maybe we can turn a disadvantage into an advantage.
“I don’t think he in particular needs a long time to adapt to our game because N’Golo is N’Golo and everybody is aware that he is a key player and needs to be a key player if you want to win big stuff.”
Kante does have the issue of under a year left to run on his contract, alongside teammates Jorginho and Marcos Alonso.
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The Blues could lose a star player for free next summer having already seen Antonio Rudiger and Andreas Christensen depart in the same circumstances this summer.
It was an issue that Tuchel has asked to be resolved under the previous owner and one he has already asked to be fixed by the new Boehly-Clearlake consortium.
“It is [an issue], but I want a lot of things,” he concluded.
“Not all things become reality but everybody is aware of the situation with only N’Golo but also Jorginho. We knew about the situation with Andreas and Toni and we don’t want this. So we are on it to solve it in the best interests of the club.”