Atletico enter the match off the back of a 2-1 win over Real Madrid at the weekend, but Simeone is under no illusions as to the size of the task this evening.
"This is going to be one of the most difficult games in the group because of who the opponents are and the atmosphere the fans generate there," he told reporters.
"But there is no euphoria [after the weekend]. We are continuing to build with the arrival of new players and trying to unite the group without changing the style."
Atletico reached the final of the Champions League last season, while Olympiacos fell at the last-16 stage.