Defending champions Sevilla were pitted against two-time winner Tottenham in Friday's draw for the UEFA Cup quarter-finals.
AZ Alkmaar were drawn against Werder Bremen, Bayer Leverkusen against Osasuna, and Espanyol against Benfica in the other two-leg quarter-finals to be played on April 5 and 12.
The semi-final draw was also made and an all-Spanish or an all-German final on May 16 in Glasgow is still possible.
The winner of Sevilla vs. Tottenham Hotspur will play Bayer Leverkusen or Osasuna next, while AZ Alkmaar or Werder Bremen will meet Espanyol or Benfica.
Sevilla made the draw after struggling to beat Shakhtar Donetsk 3-2 late on Thursday. Sevilla goalkeeper Andres Palop scored an injury-time equalizer before Javier Chevanton added the winner in extra time.
That game has boosted the club's confidence, Seville coach Juande Ramos said.
"Sevilla should [now] fear no one," Ramos said, adding that he would have preferred to play the second leg in Spain.
"The English create very good atmosphere at home, and having to play away against them means we're going to have to try to take a good first-leg result," he said.
Sevilla beat another Premier League team, Middlesbrough, in last year's final.
Tottenham, who won the UEFA Cup in 1972 and 1984, overcame an early own-goal with two goals by Bulgarian striker Dimitar Berbatov to beat Braga 3-2, and advanced 6-4 on aggregate.
"It's going to be a very spectacular game because there are two attacking teams with great forward players," said Tottenham sporting director Damien Comolli. "They are like us, they are doing well in the league and they are still in the Copa del Rey, as we are in the FA Cup."
Bremen, second in the Bundesliga behind Schalke, travel to the Netherlands for the second time in the UEFA Cup this year to face AZ for the first leg.
They beat Ajax 3-0 at home and then squeezed through after a 3-1 defeat in Amsterdam.
"So we get a Dutch team again," Bremen coach Thomas Schaaf said. "They are very strong at home and it's going to be very important to get a good result there."
AZ are also second in their domestic league, eight points behind PSV Eindhoven.
Bayer Leverkusen, the second German team still in the competition, host Spain's Osasuna.
Leverkusen, the 2002 European Champions League runners-up, reached their first UEFA quarter-final in 12 years with a 3-0 win over France's Lens, overcoming a 2-1 loss in the first leg.
Osasuna beat Rangers 1-0 for a 2-1 overall score and their first ever European quarter-final.
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