Former UEFA Cup holders Feyenoord face an uphill task to stay in this season's competition after the 2002 winners suffered a 2-0 home defeat by Czech side Teplice in the first leg of the second round on Thursday.
Borussia Dortmund, the 1997 European champions, also have work to do despite battling back from a two-goal deficit to draw 2-2 at home to Sochaux.
PHOTO: AP
There were no hiccups though for Barcelona as Frank Rijkaard's side cruised to a 3-0 away win against Greek side Panionios, while 2001 UEFA winners Liverpool take an away goal back to Anfield after a 1-1 draw with Romania's Steaua Bucharest.
Primera Liga leaders Valencia suffered a night of frustration at the Mestalla with Israel's Maccabi Haifa earning a 0-0 draw.
Teplice knocked out Germany's Kaiserslautern in the first round and the side who hail from the north west of the Czech Republic look set for another big-name scalp after victory over Feyenoord.
The Dutch side were reduced to 10 men after just two minutes when Gill Swerts was dismissed for pulling back the pacey Jan Rezek when through on goal. Michal Dolezal crashed home the resultant free kick to put Teplice ahead and Rezek added a second from close range on 57 minutes.
Dortmund, missing several first-choice players through injuries, at least avoided becoming the second German side to lose at home to French opposition in Europe in 24 hours after Bayern Munich's 2-1 Champions League defeat by Olympique Lyon on Wednesday.
Brazilian Francilendo dos Santos opened the scoring for Sochaux with an angled effort from inside the box on 12 minutes and fellow striker Pierre-Alain Frau doubled the advantage with a powerful drive from 18m 15 minutes later.
Substitute Sahr Senesie restored hope for the home side in the 68th minute and Brazilian striker Ewerthon equalized from 10m in the 76th.
Dutch striker Patrick Kluivert came off the bench to score with his first touch, netting Barcelona's second in a comfortable 3-0 win in Athens over Panionios.
It was only Kluivert's second goal of the season, his other also coming in the previous round of the UEFA Cup. Luis Garcia and Xavi also netted for Barca.
French defender Djimi Traore curled in a superb right-foot shot to give four-times European champions Liverpool an early lead against Steaua on a pitch that had cut up badly in torrential rain.
But the home side, European champions in 1986, gave themselves a fighting chance in the second leg thanks to a 69th minute equalizer from striker Claudiu Raducanu.
RC Lens defeated AC Milan in the group stages of the Champions League 12 months ago but the 1998 French champions now face elimination from the UEFA Cup after they were humbled 3-0 away at Turkey's Gaziantepspor. The hosts, who netted through Devran Ayhan, Riadh Bouazizi and Zdravko Lazarov, also missed a penalty.
Parma, UEFA winners in 1995 and 1999, romped to a 4-0 win at Austria's SV Salzburg while Serie A rivals AS Roma needed a last-minute goal from Antonio Cassano to defeat Croatia's Hajduk Split 1-0.
Perugia put their problems to one side by overcoming Aris Saloniki 2-0.
The return legs take place on Nov. 27.
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