The first round of the 2005–06 UEFA Cup was played from 15 to 29 September 2005, which narrowed clubs down to 40 teams in preparation for the group stage.
[1] All times are CET, as listed by UEFA.
2–2 on aggregate; Levski Sofia won on away goals.
1–1 on aggregate; Red Star Belgrade won on away goals.
Vitória de Guimarães won 4–0 on aggregate.
4–4 on aggregate; Halmstads BK won on away goals.
Maccabi Petah Tikva won 5–4 on aggregate.
Zenit Saint Petersburg won 1–0 on aggregate.