Mendy was dispossessed by Brenden Aaronson in front of goal in the 33rd minute for Leeds’ opener, before Rodrigo headed in a second from a 37th-minute free-kick.
The Whites rounded out the win with a third goal from Jack Harrison in the 69th minute, before Kalidou Koulibaly’s late red card.
“He knows himself. With these kind of mistakes, I don’t know if it is necessary to speak about it,” Tuchel said about Mendy.
“He knows himself and it has nothing to do with protecting him, everybody in the world sees that mistake.
“It’s a huge mistake in a crucial time in the match. He’s the one who’s the most disappointed, this cost us a lot today.”
Tuchel insisted that Chelsea’s defeat did not come from Leeds’ style, rather his own side’s wastefulness with the ball, particularly early.
“I think we lost it in the first 20 minutes,” he said.
“We created enough chances and half chances to be 1-0 or 2-0 up and then we lost the discipline, we lost the repetition in doing what we wanted to do and what we did okay in the first 20 minutes.
“This is not the story. We were not all over the place, we did not lose our discipline against the ball.
“With the ball we were not disciplined enough, we were not sharp enough after 20 minutes, but against the ball everything was fine. It was not like we could not cope with anything.
“Its a set-piece and a huge mistake and until then it should only have been one team and thats us. There was enough in the first 15 minutes to kill that game, to bring it in the minimum into the direction where it was last season, when we scored the opening chance, did what we did and had a comfortable win. It was possible.”