Unai Emery's side claimed the title with victory over Benfica last season and will need to overcome Andre Villas-Boas' men in the last eight next month to defend their crown.
Zenit are also former winners of the competition and were kept from drawing Ukrainian sides Dynamo Kiev or Dnipro due to political tensions between Russia and Ukraine.
Following their extra-time win over Ajax, Dnipro will face a Club Brugge side unbeaten in this season's competition while Kiev will take on Roma's conquerors Fiorentina.
Rafael Benitez - bidding to win the competition for a third time in its various forms - sees his Napoli side take on Bundesliga high-flyers Wolfsburg.
The ties will be played on April 16 and 23.
Draw in full:
Sevilla v Zenit
Dnipro v Club Brugge
Dynamo Kiev v Fiorentina
Wolfsburg v Napoli
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