On-loan striker Roberto Soldado gave Osasuna a narrow lead with the only goal against holders Sevilla while Espanyol moved to the brink of an all-Spanish UEFA Cup final after demolishing Werder Bremen 3-0 on Thursday.
Osasuna, the only one of the semi-finalists not to have played in, or won, a UEFA final, will take a 1-0 lead to Andalucia next week thanks to Soldado's 55th-minute goal in Pamplona.
UEFA Cup semi-finals (1st leg)
Osasuna 1 Sevilla 0
Espanyol 3 Werder Bremen 0
Soldado, who has made just a handful of first-team appearances for Real Madrid, headed in a free kick just seconds after picking up a yellow card that will rule him out of the return.
Espanyol are unlikely to start celebrating just yet despite goals from Moises Hurtado, Walter Pandiani, taking his tally to a competition-leading 11, and Ferran Corominas securing victory over Werder Bremen.
The German side had to play the majority of the second half with 10 men after keeper Tim Wiese was sent off for a professional foul.
Espanyol's joy will be tempered though after yellow cards for Hurtado and Pandiani mean they are suspended, along with Wiese, for the second leg.
The Barcelona side will also look back to 1988 as a major reason not to begin thinking of the May 16 final in Glasgow.
The Catalans beat Bayer Leverkusen 3-0 in the first leg of the UEFA Cup final that year but the trophy was snatched from their grasp when they went down 3-0 in the second leg and then lost out 3-2 to the Germans in a penalty shootout.
FEISTY ENCOUNTER
Osasuna were not overawed by Primera Liga rivals Sevilla in a feisty encounter at Reyno de Navarra that was halted for more than six-and-a-half minutes midway through the second half when Dutch referee Eric Braamhaar suffered a torn calf muscle and disappeared into the tunnel for treatment.
Braamhaar, who took charge of the controversial Champions League first-leg tie between Lille and Manchester United in February, did not re-emerge and fourth official Pieter Vink eventually took over.
Osasuna created the better openings against a subdued Sevilla, who only threatened in the closing stages but could not break through a defence keeping a clean sheet for the sixth time in their last seven UEFA Cup matches.
"We played really well," Osasuna coach Jose Angel Ziganda told a news conference. "The fans were brilliant, the players were really focused and it was a great performance.
"We know that if we are to make the final we have to play two great games. We've played one and now we have to do it again.
"We know that they can level the tie with just one goal, but if we score one next week they will have to get three to win it."
Espanyol coach Ernesto Valverde, who played in the 1988 final, said his team needed to keep their feet on the ground.
"We played some very good football and it is a great result which we would have settled for before the match," Valverde told Canal Plus television.
"But they are a very good team and we must keep our feet on the ground. We have some important players missing through suspension for the next game."
Defender Hurtado met Francisco Rufete's cross from the right with a powerful header for the opening goal on 20 minutes and Pandiani doubled the advantage with a close-range header five minutes into the second half.
Werder lost Wiese to a straight red card on 58 minutes for bringing down Raul Tamudo outside the area as the striker bore down on goal and Espanyol snatched a third with two minutes remaining through substitute Corominas.
