The Primeira Liga winners are missing three central defenders plus goalkeeper Julio Cesar for the last-16 second leg at the Petrovskiy Stadium.
Luisao and Lisandro Lopez are injured and Jardel is suspended. That leaves Victor Lindelof, who started the season as a reserve, as the only recognised central defender in the squad.
Right back Andre Almeida is also banned while Julio Cesar will be replaced by fellow Brazilian Ederson because of a thigh injury.
Benfica's record of one win, two draws and four defeats in seven visits to Russia hardly augurs well either. Their only victory came 20 years ago when they beat Lokomotiv Moscow 3-2 in the now-defunct European Cup Winners' Cup.
Coach Rui Vitoria, however, is buoyed by Saturday's 1-0 triumph at Sporting that sent his side to the top of the Portuguese league ahead of their neighbours.
"It's always better to work from the base of a win," he said.
Benfica have notched 13 victories in 14 matches this year with only a league defeat against arch-rivals Porto interrupting the sequence.
Vitoria has no worries in attack where striker Jonas has scored 28 goals in 35 games in all competitions and is enjoying the best season of his career at the age of 31.
Zenit boss Andre Villas-Boas, who faced Benfica seven times as coach of Portuguese rivals Academica Coimbra and Porto, said the supporters could lift his side to victory and a first-ever quarter-final place.
"We have the advantage going into the return leg, by this I mean our supporters," said the former Chelsea and Tottenham Hotspur supremo.
"I am sure the stadium will be packed and they will create an atmosphere which will help the team to a new level.
"We are sure we can overcome the deficit," added the Portuguese. "Reaching the quarter-finals of the Champions League is our dream and this could be a very important event for Russian football."
(Reporting by Brian Homewood, additional reporting by Dmitriy Rogovitskiy, editing by Tony Jimenez)
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