Atletico Madrid arrives at Bayer Leverkusen for Wednesday's Champions League last-16, first-leg clash hoping for a sixth straight shutout in Europe, with Mario Mandzukic and Antoine Griezmann hunting more goals.

Between them they have already tallied 37 times this season as the 2014 Champions League finalist looks to leave Leverkusen's BayArena with an advantage in the hunt for a quarterfinal place.

Former Bayern Munich striker Mandzukic has already shown Pep Guardiola what he is missing in Bavaria by scoring 20 goals, while Griezmann has hit the net 17 times.

French midfielder Griezmann said Diego Simeone's Madrid needs a good start in Leverkusen, just as it had in Saturday's 3-0 home league win over Almeria to stay third in the standings.

"We need to keep working and enjoying the games like we are at the moment," said the Frenchman after netting in the 20th and 29th minutes following Mandzukic's 13th-minute penalty.

"We need to face all the games the same way, trying to win and coming out flying from the start."

The only casualty for Madrid is midfielder Koke, who will miss the first leg with a hamstring injury having scored two goals and provided four assists in the group stages.

Olympiacos was the last team to score against Atletico when it enjoyed a 3-2 group stage win in Greece back in September.

Since then, Madrid has scored 12 goals without reply in Europe, including a 5-0 thumping of Malmo and a 4-0 thrashing of Olympiakos in the return leg.

Bayer has never won a last-16 tie in the competition's current format and will need to work hard to change that statistic against an Atletico side that finished atop Group A ahead of Juventus.

Luckless in last 16

Leverkusen is winless in its past three league matches and has had little to cheer about at this stage of the competition in recent years.

Leverkusen was thumped 4-0 at home by Paris St. Germain last season on the way to a 6-1 aggregate defeat. That came two years after Lionel Messi ran riot when Bayer's 3-1 defeat in Leverkusen preceded a 7-1 humiliation away to Barcelona in 2012 when the Argentine netted five times.

Leverkusen is without Australia winger Robbie Kruse, who has an ankle injury, while defensive midfielder Sven Bender and defender Tin Jedvaj are doubtful with knee and hamstring injuries respectively.

Having dropped to sixth in the Bundesliga after Saturday's 2-2 draw with Augsburg, qualifying for next season's Champions League is of more pressing concern than progressing in this season's edition.

"Of course I am concerned for our European qualification for next season," said Leverkusen's director of sport, Rudi Voeller.

"We have simply given too many points away this season.

"A few things aren't working as we'd like them to."

South Korea striker Son Heung-min will be looking to add to his three Champions League goals in six games so far this season, having also netted a Bundesliga hat-trick in Leverkusen's 5-4 loss to Wolfsburg two weeks ago.

Leverkusen will be without suspended defender Omer Toprak, who was sent off in its final group stage match at Benfica which ended in a scoreless draw.