The in-form Bundesliga outfit has won its last seven matches at the BayArena but its Ukrainian opponent is unbeaten in seven games in all competitions.
Bayer Leverkusen's terrific home record in the group stages of the Champions League will be tested by Shakhtar Donetsk on Wednesday.
The Germans have won their last seven fixtures at the BayArena in the group stages of Europe's premier club competition and coach Sami Hyypia will be hopeful of extending that against their Ukrainian opponent.
Leverkusen has made its best ever start to a Bundesliga season, posting seven wins in nine matches - form that sees the club sitting third in the table, just a point behind leader Bayern Munich.
The latest win was shrouded in controversy, though, with Stefan Kiessling awarded a goal for a header that ended up in the net via the side netting in a 2-1 victory at Hoffenheim on Friday.
Although Hoffenheim has called for a replay, that appears unlikely, despite Hyypia offering his apologies afterwards.
"Obviously it feels a little uncomfortable winning like that. I can't do anything about it (though). It's the referee who makes the decisions," the former Liverpool defender said.
The furore surrounding Kiessling's goal took the attention away from Leverkusen winger Sidney Sam, who capped another excellent performance with a goal.
Sam has scored 10 in 14 appearances this season, with seven coming in the Bundesliga, and his form has helped Kiessling, who had been expected to shoulder the bulk of the scoring duties this season.
Leverkusen won its last European fixture, defeating Real Sociedad 2-1 thanks to Jens Hegeler's stunning injury-time free kick, which was the club's 100th goal in the Champions League.
Lars Bender (thigh) is still an injury worry for Leverkusen, but South Korea winger Son Heung-Min will be raring to go after he was an unused substitute at Hoffenheim.
Shakhtar tops Group A with four points from two matches and will enter the match on the back of a seven-match unbeaten run in all competitions.
The Ukrainians have scored 10 goals in their last two domestic fixtures, with Argentine forward Facundo Ferreya scoring a hat trick in the 7-0 demolition of Arsenal Kiev earlier this month.
The team sits second in the league – a crown it have won seven times in the last 10 years – and has progressed through the group stages of the Champions League in the last two seasons.
Despite losing the likes of Fernandinho, Henrikh Mkhitaryan and Willian in the close season, Brazilian trio Luiz Adriano, Alex Teixeira and Douglas Costa have continued to perform for coach Mircea Lucescu.
New signings Fred and Bernard – who arrived from the Brazilian Serie A for a combined fee of more than 40 million euros – have settled well and, after snaring a point against Manchester United in their last Champions League fixture, Shakhtar will be confident of ending Leverkusen's superb home record.
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