Turkey playmaker Arda has been suffering with a bruised thigh and his absence would deprive the Spanish champions of their most creative player.
"We hope he will be fine," Simeone, who will definitely be without injured Spain midfielder Koke, told a news conference.
"Arda's characteristics are different to other team mates," added the Argentine.
"If Arda plays of course things change. With him there is one idea and without him a different one."
Atletico qualified for the knockout stage top of their group ahead of Italian champions Juventus and are looking to go one better than last season when they lost to neighbours Real Madrid in the final.
They have reached the quarter-finals of Europe's elite club competition on six previous occasions and have won five and lost only one of their Champions League away games since September 2013.
Simeone said he did not think Leverkusen's recent struggles in the Bundesliga would have much of a bearing on Wednesday's game at the Bay Arena.
The German side, who lost to Real in the 2002 Champions League final, have slipped to sixth in the domestic standings after defeats to Werder Bremen and Wolfsburg and Saturday's 2-2 draw at Augsburg.
"We are not just going on their last two matches but looking at their form from the past four months," Simeone said.
"They are attack-minded and very courageous. They are very fast and dangerous in the spaces. That is what I am focussing on and not their last two games."
Atletico and Leverkusen met home and away in the Europa League group stage in 2010-11, with each game ending 1-1.
(Writing by Iain Rogers, editing by Toby Davis)
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