Sami Hyypia's men now have a mountain to climb and go into the fixture in poor form having won only two of nine games in all competitions since the mid-season break.
In addition, PSG have a dominant record at the Parc des Princes, where the Ligue 1 leaders have suffered only one defeat since November 2012.
Laurent Blanc's men have conceded only five goals in seven European matches so far this term and have not shipped four goals since a 4-4 Ligue 1 draw with Lyon back in February 2012.
Leverkusen's task has been made harder by an injury to midfielder Jens Hegeler, who tore ankle ligaments in the 1-1 draw with Hannover last Saturday to join Robbie Kruse on their long-term injury list.
The visitors will also be without defender Emir Spahic, who is suspended after being sent off in the first leg.
By contrast, PSG should be able to welcome back Uruguay striker Edinson Cavani, who missed Saturday's 3-0 league success at Bastia to attend to a personal matter in his homeland.