Mircea Lucescu's side were thumped 4-0 in Germany on matchday three in Group A, their joint heaviest defeat in the competition and Leverkusen's biggest win in the Champions League.
The result left Shakhtar in third place, two points adrift of Leverkusen in second and three behind leaders Manchester United.
Lucescu's charges have made an indifferent start to the defence of their Ukrainian Premier League title, currently lying second in the table, two points shy of leaders Metalist, having dropped 13 points from 15 matches, already two more than in the whole of last season.
The last time Shakhtar hosted German opponents was in last season's round of 16, eventual runners-up Borussia Dortmund coming away with a 2-2 draw before sealing their place in the last eight with a 3-0 win in Germany.
Their most recent visit, in last season's Europa League group stage, ended in a 2-0 defeat to Metalist, a far cry from their visit to the same opponents in the same competition two years earlier, when they returned to Germany with a 4-0 victory.
Sami Hyypia's side have recovered well since a 4-2 defeat at Old Trafford on matchday one, seeing off Real Sociedad 2-1 at home in the next game before the win over Shakhtar.
Leverkusen's top scorer Stefan Kiessling is expected to return after being rested from the starting XI on Saturday, while Emir Spahic missed that match with a back injury suffered on the eve of the game.
