The Germans have lost nine times in their domestic campaign while dropping to eighth in the table but can take comfort from an unbeaten 10-match streak at home in Europe as they seek to advance past this knock-out stage for the first time.
Leverkusen did reach the Champions League final in 2002 where they lost to Real Madrid but at the time there was no round of 16 but only two group stages with the quarter-finals following after that.
They now hope their European form will carry them past the Spanish club that reached the final in two of the last three seasons.
"Why not win against them?" said Leverkusen goalkeeper Bernd Leno. "If we show our Champions League face, then everything is possible.
"You can see the team really wants it. We are fighting, we are fighting for each other and that was not necessarily the case a couple of weeks ago."
Leno has every right to feel confident with Leverkusen having won their last two league matches, including Friday's 3-1 victory at Augsburg, to boost their confidence and offer coach Roger Schmidt some respite.
"We are confident and want to step on the gas on Tuesday," said Karim Bellarabi, who scored the Bundesliga's 50,000th goal on Friday.
"This will be a really hard game and we are already looking forward to it. We want to get as much as possible out of it."
Atletico, who lost in the Champions League final in both 2014 and 2016 to their city rivals Real Madrid, were beaten by Leverkusen 1-0 in Germany two years ago but advanced on penalties in the return leg.
In that 2015 home game, Hakan Calhanoglu's goal earned Leverkusen their victory but the talented attacking midfielder will be watching from the stands this time.
The Turkish international is out for the rest of the season after being handed a four-month ban by international governing body FIFA over a breach of contract offence when he was at Karlsruher six years ago.
Despite their unbeaten home run, Leverkusen still have a mountain to climb against the Spaniards, who won 4-1 at Gijon on Saturday with substitute Kevin Gameiro scoring a remarkable late hat-trick in the space of less than five minutes, making it the fastest treble in La Liga since 1995.
Diego Simeone's men may not have excelled as in past seasons, having lost three of their last eight fixtures but they have yet to lose on the road this year.
They will be without defender Diego Godin, ruled out with a thigh injury but will have goalkeeper Jan Oblak back after his shoulder injury and surgery in December.
(Editing by Ian Chadband)
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