Andre Villas-Boas’s Russian league leaders travel to Spain missing no fewer than five first team regulars.
Defenders Domenico Criscito and Igor Smolnikov, skipper Miguel Danny and Brazilian star striker Hulk are all banned after collecting third bookings in the last 16 return leg against Torino.
Villas-Boas’s plight is compounded by the absence of Russian international midfielder Viktor Faizulin, recovering from knee surgery.
“We have to think hard (about our line-up on Thursday) since we have four players that are suspended and we have to think about the objective (in that match),” the Zenit boss said.
The 2008 winners face a stiff task against a Sevilla side fresh from holding Barcelona to a 2-2 draw in La Liga at the weekend.
That fightback extended their unbeaten run at home to 33 games and ensured they remain just four points adrift of Atletico Madrid in the fight for a return to the Champions League next season.
Sevilla, who claimed their third Europa League title when beating Benfica on penalties last year, will fancy their prospects of gaining an edge on Thursday ahead of next month’s return leg in Russia. They beat Zenit 5-2 at the same stage in 2006.
“Winning the Europa League for the second successive year will be very complicated,” said Fernando Navarro, the Sevilla defender and Spanish Euro 2008 winner.
Ukraine are doubly represented in the last eight by Dynamo Kiev, who ended Premier League club Everton’s ambitions in the last 16, and Dnipro Dnipropetrovsk.
Dnipro are the surprise packages this season, stunning Dutch giants Ajax to set up a last eight clash with Club Brugge of Belgium.
Dnipro owe their continued presence in the competition to the away goals rule after their last 16 tie with Ajax ended 2-2 on aggregate.
Dnipro coach Myron Markevych insisted his team must show Brugge plenty of respect after they were drawn against the Belgian outsiders.
“It’s ridiculous to say that Brugge is a good draw for us. This is a very strong, classy team that plays great attacking football and got past Besiktas so easily, which says a lot,” said the coach.
Dynamo Kiev have been ordered by UEFA to close part of their stadium for Fiorentina’s visit after racist behaviour by their fans towards Everton players last month.
The last eight line-up is completed by Wolfsburg, who brushed aside Inter Milan last month to set up a meeting on Thursday with another Serie A outfit, Rafael Benitez’s Napoli.
The 2009 German champions enjoyed their best run in the competition in 2010, when they reached the quarter-finals, while Napoli memorably won the former UEFA Cup in 1989 when Diego Maradona inspired them to a 5-4 aggregate victory over Stuttgart.
The quarter-final second legs will be played on April 23, with the final in Warsaw on May 27.
Fixtures (2005 GMT kick-offs)
Sevilla (ESP) v Zenit St Petersburg (RUS)
Club Brugge (BEL) v Dnipro Dnipropetrovsk (UKR)
Dynamo Kiev (UKR) v Fiorentina (ITA)
Wolfsburg (GER) v Napoli (ITA)