Barcelona, one of only four sides to have won all three European club competitions, believe they can score more goals away against AEK Larnaca of Cyprus after a 2-0 home win two weeks ago, both scored by Ronaldo.
"We musn't lose this game. The first goal will be very important. In the first leg, we should have scored four or five goals and I think we'll do that there," Bobby Robson, the Barcelona coach, said.
Barcelona are without their injured Spanish international midfielder Josep Guardiola, striker Juan Pizzi and defender Sergi Barjuan, but the strength in depth of their squad means the absences will hardly be noticed.
Benfica visit Ruch Chorzow of Poland with a 5-1 lead from the first leg, while PSV are level at 1-1 with Dynamo Batumi of Georgia going into their home leg.
Another former European Cup-winning team, Red Star Belgrade, are 1-0 down, but home advantage in front of a crowd expected to be almost 100,000 could help them through against Kaiserslautern.
The Germans, relegated in their cup-winning season, will be looking to their Czech Republic players, Pavel Kuka and Miroslav Kadlec, but the latter is one of several injury doubts for Otto Rehhagel, their coach. The former German international defender Andreas Brehme stands by in case Kadlec fails a late fitness test.
Kaiserslautern are bidding to become the first German Second Division side to reach the second round in European competition.
Nimes look set to become the first French Third Division side to progress beyond the first round in Europe as they defend a 3-1 lead away to Hungary's Kispest Honved.
Honved will need plenty of inspiration against Nimes, but enter the tie in optimistic mood after a 2-1 away win at the weekend when Mihaly Toth, scorer of two of their three goals in the Cup-Winners' Cup this season, hit the winner.
Toth, whose away goal at Nimes may prove useful, plays in what is expected to be an unchanged team.
France have two clubs in the Cup-Winners' Cup with the holders, Paris St-Germain, at home to Vaduz with a 4-0 lead from the first leg.
The Liechtenstein part-timers' only hope of scoring against a PSG side that has yet to concede a goal under Ricardo, their Brazilian manager, this season is if the French side tests a few inexperienced players in a tie virtually sewn up two weeks ago.
The PSG goalkeeper, Bernard Lama, is out injured, while Ricardo may rest Lama's fellow French internationals Alain Roche and Vincent Guerin.
Fiorentina are level at 1-1 going into the home leg against Gloria Bistrita of Romania thanks to Gabriel Batistuta's away goal.
Brazil's Luis Barroso Oliveira and the Italian striker Anselmo Robbiati will line up alongside Batistuta, the Argentinian international striker.
The same trio led Fiorentina to a 2-0 win over Verona on Sunday - their first league victory of the season.
"A three-pronged attack can go well both both for home and away games," Claudio Ranieri, the Fiorentina coach, said.
"But we're cautious - everyone thinks we're already through to the next round and are only talking about our league game next Sunday against Juventus. But the truth is Gloria Bistrita are a dangerous team."
Portugal's Manuel Cesar Rui Costa is expected to play behind the front three, in the role of playmaker.
Sparta Prague have two away goals from a first leg 2-2 draw with Sturm Graz of Austria going into the home leg, but their coach, Jozef Chovanec, has warned his team against complacency.
"We have the chance to move to the second round in our hands and we can't let it slip out with a defensive mistake. We can't let down our guard, even for a second," he said.
Chemlon Humenne of Slovakia, playing in Europe for the first time, are 1-0 down against AEK Athens, despite dominating much of the away leg.
"In Athens, we put up a fight and attacked constantly, although we could not get the equaliser. On Thursday we will do the same," their coach, Ondrej Danko, said.
Away goals could also stand Brann Bergen of Norway in good stead as they face Cercle Bruges of Belgium 3-2 down.