While he stressed that he respected the Serb as a person and player, Nadal made it clear no one was bigger than the sport.
"I tell you one thing, it's very clear that Novak Djokovic is one of the best players of the history, without a doubt. But there is no one player in history that's more important than an event, no?" he said.
"The players stay and then go, and other players are coming. No one, even Roger (Federer), Novak, myself, Bjorn Borg who was amazing at his times, tennis keep going.
"The Australian Open is much more important than any player," he added.
"If he's playing finally, okay. If he's not playing, Australian Open will be great Australian Open with or without him."
Nadal added that the saga had gone "too far" and he was "a little bit tired of the situation because I just believe that it's important to talk about our sport, about tennis".
Defending Australian Open champion Naomi Osaka said she didn't know the Serbian well, but was sad that he might now be remembered more for his anti-vaccination stance than his exploits on the court.
'Australians have gone through a lot'
"I think it's an unfortunate situation. He's such a great player and it's kind of sad that some people might remember (him) in this way," she said, two days before the start of the tournament.
World number four Stefanos Tsitsipas criticised the 20-time Grand Slam winner earlier this week, saying he was "playing by his own rules".
But he was reluctant to get involved again on Saturday.
"I'm here to talk about tennis, not Novak Djokovic," said the Greek 23-year-old.
"I won't lie. It has been pretty much on every news outlet the last couple of weeks. It has received a lot of attention. A lot of people are obviously talking about it.
"That's why I'm here to talk about tennis. Not enough tennis has been talked about in the last couple of weeks, which is a shame."
But Djokovic did win cautious support from world number three Alexander Zverev, who suggested Djokovic was being made an example of.
"I think Novak is a very big name, a global superstar. I think that he is someone that maybe people think they can make a big deal out of it just because it's Novak," he said.
"I don't know enough of the situation, but I do think if it would not be Novak Djokovic, world number one, with 20 Grand Slams, all that, then it would not be as big of a drama. That I do believe," he added.
But Australia's main men's hope Alex de Minaur was fed up, saying it was detracting from the tournament and other players.
"First of all, this whole situation has taken a lot of spotlight away from us competitors. We're here to play the Australian Open,” he said.
"It feels like it's taking away from us competitors who just want to start."
Pressed on whether Djokovic had been the author of his own demise, he replied: "Look, Australians have gone through a lot. There's no secret about that. They've had it very tough.
"They've done a lot of work to protect themselves and their borders. When you're coming in, as well as every other tennis player, if you wanted to come into the country, you had to be double-vaccinated."
Former world number one Andy Murray, who will play at the Open, said he hoped Djokovic's status would be cleared up, but he added: "I'm not going to sit here and start kicking Novak whilst he's down."