The second round of the 1999–2000 UEFA Cup began on 19 October 1999. The round included 48 winners from the first round.
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2–2 on aggregate; AEK Athens won on away goals.----Bologna won 4–2 on aggregate.----Wolfsburg won 1–0 on aggregate.----Udinese won 2–1 on aggregate.----Monaco won 3–1 on aggregate.----Deportivo La Coruña won 5–1 on aggregate.----Roma won 3–0 on aggregate.----2–2 on aggregate; Werder Bremen won on away goals.----Slavia Prague won 3–2 on aggregate.----Parma won 4–1 on aggregate.----Leeds United won 7–1 on aggregate.----Atlético Madrid won 5–1 on aggregate.----Nantes won 7–0 on aggregate.----2–2 on aggregate; Panathinaikos won away goals.----Lens won 5–2 on aggregate.----Ajax won 3–1 on aggregate.----3–3 on aggregate; Benfica won 4–1 on penalties.----Kaiserslautern won 2–1 on aggregate.----Lyon won 2–0 on aggregate.----Juventus won 4–2 on aggregate.----Newcastle United won 5–2 on aggregate.----Steaua București won 2–0 on aggregate.----Celta Vigo won 4–2 on aggregate.----Mallorca won 5–1 on aggregate.