| Ties will be played on September 18 and October 2, 2008. | |
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| FC Timisoara (ROU) | v | FK Partizan (SRB) | |
| AC Milan (ITA) | v | FC Zürich (SUI) | |
| Hertha Berlin (GER) | v | St Patrick's Athletic (IRL) | |
| Baník Ostrava (CZE) | v | Spartak Moskva (RUS) | |
| Metalist Kharkiv (UKR) | v | Besiktas (TUR) | |
| Portsmouth (ENG) | v | Vitória SC (POR) | |
| Kayserispor (TUR) | v | Paris St Germain (FRA) | |
| FC Sevilla (ESP) | v | FC Salzburg (AUT) | |
| VfL Wolfsburg (GER) | v | Rapid Bucharest (ROU) | |
| Sampdoria (ITA) | v | FBK Kaunas (LTU) | |
| Marítimo (POR) | v | Valencia CF (ESP) | |
| Dinamo Zagreb (CRO) | v | Sparta Prague (CZE) | |
| Manchester City (ENG) | v | Omonia (CYP) | |
| Young Boys (SUI) | v | Club Brugge (BEL) | |
| AS Nancy-Lorraine (FRA) | v | Motherwell (SCO) | |
| Everton (ENG) | v | Standard Liege (BEL) | |
| Napoli (ITA) | v | Benfica (POR) | |
| Bellinzona (SUI) | v | Galatasaray (TUR) | |
| NEC Nijmegen (NED) | v | Dinamo Bucharest (ROU) | |
| Racing Santander (ESP) | v | FC Honka (FIN) | |
| APOEL (CYP) | v | Schalke 04 (GER) | |
| Litex Lovech (BUL) | v | Aston Villa FC (ENG) | |
| Austria Vienna (AUT) | v | Lech Poznan (POL) | |
| Vitória FC (POR) | v | Heerenveen (NED) | |
| SK Brann (NOR) | v | Deportivo La Coruña (ESP) | |
| Slavia Prague (CZE) | v | Vaslui (ROU) | |
| Slaven Koprivnica (CRO) | v | CSKA Moskow (RUS) | |
| Brøndby IF (DEN) | v | Rosenborg BK (NOR) | |
| Cherno More Varna (BUL) | v | VfB Stuttgart (GER) | |
| Stade Rennes (FRA) | v | FC Twente (NED) | |
| Ajax Amsterdam (NED) | v | FK Borac (SRB) | |
| Tottenham Hotspur (ENG) | v | Wisla Kraków (POL) | |
| FC Copenhagen (DEN) | v | FC Moskow (RUS) | |
| M`K }ilina (SVK) | v | Levski Sofia (BUL) | |
| Borussia Dortmund (GER) | v | Udinese (ITA) | |
| SC Braga (POR) | v | Artmedia Petr~alka (SVK) | |
| Feyenoord (NED) | v | Kalmar (SWE) | |
| Hamburg (GER) | v | Unirea Urziceni (ROU) | |
| Hapoel Tel-Aviv (ISR) | v | Saint Etienne (FRA) | |
| FC Nordsjælland (DEN) | v | Olympiakos (GRE) |
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