Of the nine former UEFA Cup winners vying to reach the group stage, Feyenoord are most at risk of an early exit on Thursday as they try to overturn a 1-0 first-leg home defeat by Swedish league leaders Kalmar.
The Rotterdam side, UEFA Cup winners in 1974 and 2002, conceded a second-half winner at De Kuip, a result that has added to a frustrating start for new Feyenoord manager Gertjan Verbeek.
Feyenoord have begun their league campaign with just one win from four matches and Verbeek has had to cope with a lengthy early-season injury list.
The coach has more injury concerns for the trip to Sweden. Goalkeeper Henk Timmer is doubtful after hobbling off with a hip injury in the second-half of Sunday's defeat by Groningen while experienced defender Theo Lucius is out after breaking a toe in training.
Kalmar beat second-placed Elfsborg 2-1 on Sunday and hold a four-point advantage with six games to play as they seek a first top-flight title in their 98-year history.
Tottenham Hotspur manager Juande Ramos is also feeling the strain after a sorry start to the Premier League campaign and the Spaniard, who led Sevilla to back-to-back UEFA Cup wins in 2006 and 2007, will face calls for his exit if his side fail to defend a 2-1 lead in Poland against Wisla Krakow.
Spurs, first winners of the UEFA Cup in 1972, are rooted to the foot of the Premier League after six games.
Asked if he had the confidence of his employers following the weekend defeat by Portsmouth, Ramos told the BBC: "Absolutely, we speak regularly and everyone is aware of our delicate position. But whether I survive is for the chairman and the board to decide.
Krakow showed enough attacking intent in the first leg at White Hart Lane to suggest that Spurs will face a tough afternoon in Poland.
Seven-times European champions AC Milan have hit their stride after a slow start and hold a 3-1 advantage for their trip to FC Zurich.
Milan have won three consecutive Serie A games, including a 1-0 win over city rivals Inter Milan on Sunday, and should be too strong for the Swiss side.
Ajax Amsterdam and Schalke 04 should comfortably progress, the Dutch and German heavyweights defending 4-1 leads when they host Serbia's FK Borac and Cypriot Cup holders APOEL FC respectively.
Forty teams progress to the group stage, the draw for which takes place in Nyon on Oct 7.