Thibaut Pinot is Nibali's closest rival for the yellow jersey with three stages to go, seven minutes 10 seconds behind the Italian.
Behind Pinot is fellow Frenchman Jean-Christophe Peraud (+7:23), while Spaniard Alejandro Valverde is two seconds further back in fourth.
Despite leading the charge for a maiden Tour podium, Pinot conceded he would be lucky to be standing on the dais on the Champs-Elysees.
"There are now just 15 seconds separating second place and fourth place, and I'm probably the least accomplished time trialist between the three of us," Pinot said, ahead of Saturday's 54-kilometre individual time trial from Bergerac to Perigueux.
"I'll have to have a great day to hold off Peraud, who is very good against the clock, while Valverde is of course the current Spanish time-trial champion."
Pinot went further, ruling out Friday's and Sunday's stages as chances to gain time - putting all emphasis on the time trial.
"The time trial is now going to be decisive for the podium," continued Pinot.
"I know that I've got better against the clock, although I've not had any recent references in time trials over 50 kilometres.
"But I've finished in the top 10 in time trials at the Tour of the Basque Country, the Tour of Romandie and the Tour of Switzerland this year, so I've definitely improved.
"To be in second place now on Thursday, and probably still on Friday evening [after what is a flat 19th stage] is great, but what counts is Sunday evening in Paris.
"I mustn't waste all the good work we've done since the start of the Tour to get me into this position, as I have no desire to finish on the bottom step of the podium."
Peraud said he was wary of losing time in the podium battle, on Thursday's 145.5km stage from Pau to Hautacam.
"Normally I’m a bit better than Thibaut in a time trial, so I believe in my chances for the podium. I believe in second place," Peraud said.
"When I was really in the red, I thought about this podium and I didn't want to leave Thibaut get away."