Having already sealed top spot in Group G in the UEFA Champions League, Simeone has opted to rest several of his stars for Tuesday's clash.
Talented attackers David Villa, Diego Costa and Arda Turan are among the senior stars left out of the squad.
But Simeone played down the importance around the changes and said the focus should be on the players in the team.
"It does not matter if we have gone through or not, nor the way we've played before," the Argentine said on Monday.
"What is important is the game itself and not what is happening around it. The main thing is that on the pitch we show the hunger to win and the desire to play classy football.
"We always believe in playing the best team that can compete. I remember back in the Europa League in Israel playing a certain Diego Costa. And now we see what a player he is.
"Now there are other players who want to contribute. We do not look at the names, we look at the work."
Simeone explained the changes and said there was no need to risk players, especially so soon after the international break.
"Why the changes? I am the coach and I have the ability to judge who is in better shape for this match," he said.
"But also, do not underestimate those who are here. All of our staff without exception are doing a great job."
Asked how his players would deal with the expected temperature in the minuses, Simeone said: "We will have to run. That is the best way not to feel the cold."
Simeone warned his side not to focus on Zenit striker Hulk, who stood out when the teams met on September 18 in a 3-1 win for Atletico.
"Hulk is not Zenit's only strong player. Our opponents have a strong attack made up of internationals," Atletico's coach said.
"Zenit have strong, rapid transition from defence to attack, that could create problems for us. I cannot say which team is better, Porto or Zenit (who are fighting for second place in the group)."
