Having romped to a 4-2 victory in Germany in the first-leg, Atletico have a clear advantage, especially after their talisman back in form.
Leverkusen look to extend unbeaten streak against Atletico
Frenchman Griezmann has six goals in his last seven games, with his 84th minute strike helping the Rojiblancos to a 1-0 win at Granada on Saturday.
Spain media reported that the player has decided to stay with Atletico next season despite strong interest from the Premier League, helping the club's transition from the Vicente Calderon to their new stadium, the Wanda Metropolitano.
"I am always asked the same question and I am pretty sick of it, but like I always say, I am very happy here," the 25-year-old striker told TVE.
Atletico weather late storm to seal advantage against Leverkusen
With Griezmann focused and firing after a spell between November and December in which he only found the net once in eight games, Atletico look a formidable prospect again.
However, they will be without central midfielder Gabi and left-back Filipe Luis, who are suspended, as well as injured duo midfielders Tiago Mendes and Augusto Fernandez.
Forward Fernando Torres has returned to training following the head injury he suffered against Deportivo on March 2.
This could be a decisive week in Atletico’s season as they bid to join Real Madrid and Barcelona in the next round of the Champions League before hosting third-placed Sevilla in La Liga on Sunday.
New Leverkusen coach Tayfun Korkut, appointed in place of Roger Schmidt last week, insists his team will not lose the second leg.
"We have seen in the last few days what can happen in football," he told Marca. "We will not be beaten in Madrid, we will go and fight in the tie until the end. We know what result we need to reach the quarters."
Defender Omer Toprak misses the game after suffering an ankle problem in Friday's 1-1 draw with Werder Bremen, adding to the absences of the suspended Benjamin Henrichs and the injured Jonathan Tah.
The Germans hope to have goalkeeper Bernd Leno back after he underwent nose surgery at the weekend.
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