Olympiacos will be toughest tie - Simeone
The Spanish champions made it to the final last season, but lost 4-1 to city rivals Real Madrid in extra time.
Simeone's men, who have been drawn alongside Olympiacos, Juventus and Malmo in Group A, come into their European opener on the back of a 2-1 league win over Real, but the Argentine insists the fixture will be far from straightforward.
"We have had a short time to prepare after the match against Real Madrid at the weekend," he said.
"This will probably be the most difficult game in the group; Olympiacos have a very strong home record and passionate fans."
Despite an impressive triumph at Real at the weekend, Simeone insists his close-season acquisitions, who include Mario Mandzukic, Antoine Griezmann and Alessio Cerci, are still finding their feet in his team.
"I always look at the reality of each situation," he continued. "We are building this team. Some players left, some came in.
"We are trying to familiarise them with the team's philosophy, which will not change. The team will be built around our core philosophy.
"We had a great season last year. But that's in the past. We are starting from scratch again. We are building the team day-by-day."