Germany has five teams in contention in the last 32 including four of the current top five in the Bundesliga, while England (3), Spain (3) and Portugal (3) are also well represented.
League leaders Bayern Munich visit injury-hit Scottish side Aberdeen in one of Thursday's first-leg matches, the same day that SV Hamburg travel to Zurich and Nuremberg are at Portugal's Benfica.
Bayern, four-time European champions and 1996 UEFA Cup winners, should prove too strong for Aberdeen whose manager Jimmy Calderwood is facing the loss of up to five players through injury.
Aberdeen are hoping to repeat a quarter-final victory over the Bundesliga leaders 25 years ago on their way to lifting the Cup Winners' Cup.
"We'll patch up the team as best we can, get the best 11 on the park and show them we're no pushovers," Calderwood said.
Nuremberg will have new coach Thomas von Heesen on the bench for the first time after the sacking Monday of Hans Meyer, who had taken the club into the competition by virtue of last season's German Cup triumph.
Meanwhile Bayer Leverkusen are at Turkish side Galatasary on Wednesday while Werder Bremen entertain Portugal's Braga.
Bremen's personnel problems have eased with the return of strikers Boubacar Sanogo from the Africa Cup of Nations, Hugo Almeida (Bundesliga suspension) and Ivan Klasnic (injury), while defender Naldo (Bundesliga suspension) is also available.
Leverkusen coach Michael Skibbe also welcomes back key players from injury or Africa Cup duty for the tough trip to Istanbul.
He comes up against a Bundesliga veteran in Galatasary coach Karl-Heinz Feldkamp, 73, who was in charge of Borussia Dortmund, Eintracht Frankfurt and Kaiserslautern among others.
Galatasary and Leverkusen are among six former winners including Bayern, PSV Eindhoven, Anderlecht and Tottenham Hotspur, one of the three English sides in contention.
Two-time winners Tottenham, who are at Czech side Slavia Prague on Thursday, are looking to become the fourth three-time champions after Liverpool, Inter Milan and Juventus.
Their manager Juande Ramos, who has already faced Slavia this season in the Champions League while he was coach of Sevilla, is also aiming for an unprecedented third successive UEFA Cup, having won with Sevilla in 2006 and 2007.
Everton, who have climbed to fourth in the Premier League, are at Norway's Brann Bergen, while Bolton Wanderers, struggling near the bottom, come against Atletico Madrid, fourth in Spain.
Bolton manager Gary Megson admits that Premier League survival is more important than the UEFA Cup but feels the experience of his veteran Spanish midfielder Ivan Campo could help the team upset Atletico.
Campo did not feature in the early stages of the competition after not being registered by previous manager Sammy Lee.
"Ivan was not in the original squad for the UEFA Cup games, but someone of his experience will be vital," Megson told British media.
"Being a former Real Madrid player he's been pestering me ever since we got drawn against Atletico Madrid, but it wasn't a difficult decision to make. It will be a special occasion for him."
Spain's other two representatives are also on the road for the first-leg matches, Villareal at Zenit St Petersburg and Getafe at AEK Athens, both on Wednesday.
In other games on Wednesday, Glasgow Rangers host Greece's Panathinaikos, Anderlecht meet Girondins Bordeaux, fellow French side Olympique Marseille entertain Spartak Moscow, Portugal's Sporting Lisbon are at home to Swiss outfit Basel, and remaining Dutch hopes PSV Eindhoven meet visiting Swedish side Helsingborgs.
Among the six matches on Thursday, Italy's lone representative Fiorentina travel to Norway's Rosenborg Trondheim.
The return legs are being played on Thursday February 21 with the Round of 16 matches on March 6 and March 12 and 13 on the road to the final in Manchester on May 14.