The first round of the 2005–06 UEFA Cup began on 15 September 2005, which narrowed clubs down to 40 teams in preparation for the group stage.
Seeding
Summary
First leg
All times CET
| APOEL  | 0–1 | |
|---|---|---|
| Report | Marcelinho  | 
| Baník Ostrava  | 2–0 | |
|---|---|---|
| Klimpl  Magera  | 
Report | 
| Bayer Leverkusen  | 0–1 | |
|---|---|---|
| Report | Todorov  | 
| Bolton Wanderers  | 2–1 | |
|---|---|---|
| Diouf  Borgetti  | 
Report | Jančevski  | 
| CSKA Moscow  | 3–1 | |
|---|---|---|
| Gusev  Carvalho  | 
Report | Pimpong  | 
| Grasshoppers  | 1–1 | |
|---|---|---|
| Salatić  | 
Report | Marco Manso  | 
| Graz  | 0–2 | |
|---|---|---|
| Report | Pagis  Lacour  | 
| Vitória de Guimarães  | 3–0 | |
|---|---|---|
| Cléber  Mário Sérgio Benachour  | 
Report | 
| Halmstad  | 1–2 | |
|---|---|---|
| Þorvaldsson  | 
Report | Wender  Deivid  | 
| Hamburg  | 1–1 | |
|---|---|---|
| Van der Vaart  | 
Report | Van Heerden  | 
| Krylya Sovetov Samara  | 5–3 | |
|---|---|---|
| Leilton  Adamu Kowba Husin Bober  | 
Report | Vlaar  Perez Van Galen  | 
| Litex Lovech  | 2–2 | |
|---|---|---|
| Venkov  Novaković  | 
Report | Daerden  Stojanović  | 
| Maccabi Petah Tikva  | 0–2 | |
|---|---|---|
| Report | Vukčević  Radonjić  | 
| Middlesbrough  | 2–0 | |
|---|---|---|
| Boateng  Viduka  | 
Report | 
| PAOK  | 1–1 | |
|---|---|---|
| Salpingidis  | 
Report | Shyshchenko  | 
| Slavia Prague  | 2–0 | |
|---|---|---|
| Hrdlička  Piták  | 
Report | 
| Tromsø  | 1–0 | |
|---|---|---|
| Szekeres  | 
Report | 
| Viking  | 1–0 | |
|---|---|---|
| Mumba  | 
Report | 
| Vitória de Setúbal  | 1–1 | |
|---|---|---|
| Hempel  | 
Report | Flachi  | 
Second leg
All times CET
| Hertha BSC  | 3–1 | |
|---|---|---|
| Marcelinho  Rafael Cairo  | 
Report | Makrides  | 
Hertha BSC won 4–1 on aggregate.
| Levski Sofia  | 1–0 | |
|---|---|---|
| Koprivarov  | 
Report | 
2–2 on aggregate; Levski Sofia won on away goals.
| Heerenveen  | 5–0 | |
|---|---|---|
| Samaras  Nilsson Huntelaar Yıldırım  | 
Report | 
Heerenveen won 5–2 on aggregate.
| Široki Brijeg  | 0–1 | |
|---|---|---|
| Report | Petrić  | 
Basel won 6–0 on aggregate.
| CSKA Sofia  | 1–0 | |
|---|---|---|
| Hdiouad  | 
Report | 
CSKA Sofia won 2–0 on aggregate.
Beşiktaş won 4–2 on aggregate.
| Lokomotiv Plovdiv  | 1–2 | |
|---|---|---|
| Iliev  | 
Report | Tunchev  Nolan  | 
Bolton Wanderers won 4–2 on aggregate.
Brøndby won 3–2 on aggregate.
| Braga  | 1–1 | |
|---|---|---|
| Jaime Júnior  | 
Report | Purović  | 
1–1 on aggregate; Red Star Belgrade won on away goals.
| Midtjylland  | 1–3 | |
|---|---|---|
| D. Nielsen  | 
Report | Carvalho  Samodin  | 
CSKA Moscow won 6–2 on aggregate.
| Everton  | 1–0 | |
|---|---|---|
| Cahill  | 
Report | 
Dinamo București won 5–2 on aggregate.
| Rapid București  | 1–0 | |
|---|---|---|
| Buga  | 
Report | 
Rapid București won 2–1 on aggregate.
Espanyol won 3–1 on aggregate.
| Marseille  | 0–0 (a.e.t.) | |
|---|---|---|
| Report | ||
| Penalties | ||
| Giménez  André Luís Taiwo Nasri  | 
4–1 | |
0–0 on aggregate; Marseille won 4–1 on penalties.
Grasshoppers won 4–1 on aggregate.
Strasbourg won 7–0 on aggregate.
Vitória de Guimarães won 4–0 on aggregate.
| Sporting CP  | 2–3 (a.e.t.) | |
|---|---|---|
| Wender  Žvirgždauskas  | 
Report | Þorvaldsson  Žvirgždauskas Ingelsten  | 
4–4 on aggregate; Halmstad won on away goals.
| Copenhagen  | 0–1 | |
|---|---|---|
| Report | Van der Vaart  | 
Hamburg won 2–1 on aggregate.
| Dnipro Dnipropetrovsk  | 5–1 | |
|---|---|---|
| Nazarenko  Shershun Shelayev Melaschenko  | 
Report | Riordan  | 
Dnipro Dnipropetrovsk won 5–1 on aggregate.
| AZ  | 3–1 | |
|---|---|---|
| Van Galen  Koevermans Landzaat  | 
Report | Adamu  | 
6–6 on aggregate; AZ won on away goals.
| Dyskobolia Grodzisk  | 2–4 | |
|---|---|---|
| Sedláček  Sáblík  | 
Report | Cousin  Dindane Lachor  | 
Lens won 5–3 on aggregate.
| Genk  | 0–1 | |
|---|---|---|
| Report | Sandrinho  | 
Litex Lovech won 3–2 on aggregate.
| Partizan  | 2–5 | |
|---|---|---|
| Radonjić  | 
Report | Mashiah  Golan Edri  | 
Maccabi Petah Tikva won 5–4 on aggregate.
Middlesbrough won 2–0 on aggregate.
Monaco won 5–1 on aggregate.
| Anorthosis Famagusta  | 0–4 | |
|---|---|---|
| Report | Caracciolo  Makinwa Santana  | 
Palermo won 6–1 on aggregate.
| Metalurh Donetsk  | 2–2 | |
|---|---|---|
| Kosyrin  Shyshchenko  | 
Report | Salpingidis  Konstantinidis  | 
3–3 on aggregate; PAOK won on away goals.
Rennes won 3–1 on aggregate.
Roma won 5–1 on aggregate.
Sevilla won 2–0 on aggregate.
| Debrecen  | 0–2 | |
|---|---|---|
| Report | Brandão  Elano  | 
Shakhtar Donetsk won 6–1 on aggregate.
| Lokomotiv Moscow  | 3–2 | |
|---|---|---|
| Loskov  Asatiani Bilyaletdinov  | 
Report | Macallister  Miller  | 
Lokomotiv Moscow won 5–3 on aggregate.
| Cork City  | 1–2 | |
|---|---|---|
| O'Callaghan  | 
Report | Piták  Vlček  | 
Slavia Prague won 4–1 on aggregate.
| Galatasaray  | 1–1 | |
|---|---|---|
| Şükür  | 
Report | Ademolu  | 
Tromsø won 2–1 on aggregate.
Steaua București won 6–1 on aggregate.
| Domžale  | 1–0 | |
|---|---|---|
| Stevanović  | 
Report | 
Stuttgart won 2–1 on aggregate.
2–2 on aggregate; Viking won on away goals.
Sampdoria won 2–1 on aggregate.
Zenit Saint Petersburg won 1–0 on aggregate.
- Notes
 
- Note 1: Maccabi Petah Tikva played their home matches at Ramat Gan Stadium in Tel Aviv District instead of their regular stadium, Municipal Stadium, Petah Tikva.