Seville duo Real Betis and Sevilla are keen to get through as a way of distracting their volatile fans from problems in La Liga.
Betis, who seem doomed to another relegation, go deep into Russia to face Rubin Kazan, who battled out a 1-1 draw in the first leg in Spain.
The Betis players are not keen on the prospect of playing on an artificial pitch in Russia, as midfielder Lolo Reyes pointed out Tuesday. "UEFA really should not permit artificial pitches to be used in a competition as important as the Europa League. It will be very difficult for us out there.
"We want to do well in the competition to make up for our bad domestic form. However, it looks like it's going to be a difficult experience for us." Sevilla are at home to Maribor after a 2-2 draw in Slovenia. They are without Denis Cheryshev, though Nico Pareja and Jose Antonio Reyes should be fit after overcoming recent muscle problems.
Spain's third team in the competition, Valencia, should have an easier time of things at home to Dynamo Kiev, after winning the first leg 2-0 in neutral Cyprus.
Coach Juan Antonio Pizzi will be tempted to ring the changes, giving a rare start to youngsters like Ruben Vezo and Paco Alcacer.
Tottenham manager Tim Sherwood could welcome back Sandro from injury for his side's home leg against Dnipro as the Londoners look to overcome a 1-0 deficit.
The midfielder has missed the past 14 games because of a calf injury but Sherwood believes he could play a part.
"Sandro is looking good," he said. "We have to be cautious with him because he's broken down before but he's done more training than he's done previously and we believe he's ready." Swansea had a goalless draw at home to Napoli and manager Gary Monk hopes midfielder Jonjo Shelvey can recover from a hamstring injury in time for the trip to Italy.
Shelvey was taken off at half-time in the weekend defeat at Liverpool but is expected to be fit.
Swansea defender Angel Rangel believes the Welsh side have a chance to cause a big shock by winning away to Napoli on Thursday.
"Anything is possible," he said. "Keeping a clean sheet in the first leg was very pleasing and it means we have everything to play for in the second leg.
"In Italy it will be very difficult and I'm sure it will be an intimidating atmosphere but if we play with the same resilience and quality then we have a chance.
With home advantage, Napoli will look to get the victory which will secure their place in the next round.
"We must defeat Swansea," said Slovak midfielder Marek Hamsik, who is regaining top form after a poor spell.
"Anyone (of us) can score. Getting goals is not an issue for me. The important thing is that I feel better now." Bulgarian league leaders Ludogorets have the upper hand on Lazio after beating them 1-0 in Rome.
"Now let's try to keep going in the Europa League," Lazio coach Edy Reja said after a 3-2 weekend win over Serie A strugglers Sassuolo.
"We will see how it goes, we hope to make it. If (Miroslav) Klose has no physical problems he plays. He does not look like a weakling to me." Juventus and Fiorentina are the best placed of the Italian teams to proceed into the round of 16.
The Serie A champions travel from Turin to Turkey with a 2-0 lead over Trabzonspor, while Fiorentina welcome Esbjerg after beating them 3-1 in Denmark.
Eintracht Frankfurt, the sole German side remaining in the competition, will look to complete the job after claiming a highly creditable 2-2 draw away to Porto.
The Portuguese hosts led 2-0 only for the guests to fight back and the tie is now finely balanced.
In other games, Genk host Anzhi, Lyon face Chornomorets and Maccabi Tel Aviv travel to Basel after all three first legs ended goalless.
Alkmaar and Benfica look to defend narrow away wins at home to Liberec and PAOK respectively but Salzburg can be confident of progressing after winning their first leg 3-0 at Ajax.
