The second round of the 2000–01 UEFA Cup began on 23 October 2000. The round included 48 winners from the first round.
Seeding
Matches
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1 This 2nd leg match in Vigo actually ended with the score 5–3 for the hosts Celta, but was later officially recorded as 3–0 walkover since it was discovered that Red Star fielded two suspended players.
First leg
Second leg
Kaiserslautern win 5-4 on aggregate
Osijek win 4-1 on aggregate
PAOK win 3–1 on aggregate
Werder Bremen win 9–3 on aggregate
1860 München win 5–4 on aggregate
AEK Athens win 6–2 on aggregate
Hertha BSC win 4–2 on aggregate
Alavés win 5–3 on aggregate
1–1 on aggregate. Internazionale win on away goals
Bordeaux win 3–2 on aggregate
Espanyol win 4–1 on aggregate
Roma win 2–1 on aggregate
Stuttgart win 3–2 on aggregate
Celta were awarded a 3–0 victory for the second leg as Red Star fielded ineligible players, therefore winning 3–1 on aggregate