The small side from southern Madrid caused a huge upset as they knocked Real out of the competition at the quarter-final stage last season, winning 2-1 at the Bernabeu -- their first ever victory at the stadium -- to advance on away goals after the first leg had finished 1-0 to Real.
Elsewhere Atletico Madrid will face Girona, a side coach Diego Simeone has never beaten, drawing all three meetings with the Catalans in his seven years at the helm.
Holders Barcelona will face Levante, while Athletic Bilbao take on Sevilla in the pick of the round.
The draw in full: Real Madrid v Leganes, Getafe v Valladolid, Betis v Real Sociedad, Levante v Barcelona, Athletic v Sevilla, Sporting v Valencia, Girona v Atletico Madrid, Villarreal v Espanyol.
The first legs will be played on 9 January and the returns a week later on 16th.
(Reporting by Joseph Cassinelli; editing by Martyn Herman)
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