Leverkusen sit third in the early Bundesliga table, and made a superb start to life under Roger Schmidt in scoring 22 goals in their first six competitive fixtures of the season in all competitions.
Their goals have dried up somewhat in recent weeks, however, and Schmidt's side lost 1-0 at Monaco in their Group C opener a fortnight ago - Joao Moutinho striking for the French side after Leverkusen had missed a host of chances.
Leverkusen were also kept at bay by Freiburg in a 0-0 draw last Saturday, but displayed impressive resilience to take a point from a fiery clash in which defender Emir Spahic saw red after just 28 minutes.
Schmidt believes that Leverkusen's performance at the Mage Solar Stadion shows that they have the endurance to cope with the rigours of continental competition.
"It's a good sign that the team is in good shape physically," Schmidt said.
"The energy levels are full and that's good to know ahead of such an important game."
Leverkusen, Champions League runners-up in 2002, have never beaten Benfica in their four previous meetings.
Yet they have good reason to be confident of bouncing back versus Jorge Jesus' team, who have been superb in the Primeira Liga but displayed worrying signs of fallibility in their group opener with Zenit.
The Portuguese champions were undone by their Russian opponents at Estadio da Luz as Hulk opened the scoring before midfielder Axel Witsel came back to haunt his former club with a goal to seal a 2-0 success.
Respective opening-round defeats have left Leverkusen and Benfica in need of victory to avoid the danger of becoming cut adrift at the bottom of the group, but both head into Wednesday's contest at the BayArena with absentees in key areas.
Benfica will have to cope without goalkeeper Artur after he was sent off in the reverse against Zenit and, with deputies Julio Cesar (leg) and Paulo Lopes (calf) both struggling with injuries, 19-year-old Bruno Varela is expected to make his debut for the two-time European champions.
Meanwhile, playmaker Gonzalo Castro - who missed the stalemate with Freiburg - is a doubt for Leverkusen due to a thigh complaint.
Captain Simon Rolfes and attacking midfielder Julien Brandt are both on the sidelines because of ankle injuries and defender Kyriakos Papadopoulos has a shoulder problem.
