Barcelona have been handed a tricky last-16 tie with Catalan rivals Espanyol in the Copa del Rey, while Cadiz - who progressed due to Real Madrid's expulsion - will face Celta Vigo.
Holders Barca last met Espanyol in the Copa in the 2008-09 season, when - under the stewardship of Pep Guardiola - they secured a 3-2 aggregate victory en route to winning the trophy.
Cadiz lost the first leg of their round-of-32 tie against Real 3-1, but Rafael Benitez's side were expelled from the competition after fielding the ineligible Denis Cheryshev - who had yet to serve a ban from his time playing for Villarreal last season.
In Celta, Cadiz face a side that have lost just three times in La Liga this campaign and sit fourth having taken 28 points from 15 matches.
Other notable ties see fierce rivals Sevilla and Real Betis go head-to-head while there is another city derby as Atletico Madrid play Rayo Vallecano.
Last season's runners-up Athletic Bilbao face European hopefuls Villarreal, Gary Neville's Valencia take on Granada and second-tier Mirandes were drawn against Deportivo La Coruna.
Draw in full:
Barcelona v Espanyol, Valencia v Granada, Mirandes v Deportivo La Coruna, Cadiz v Celta Vigo, Real Betis v Sevilla, Villarreal v Athletic Bilbao, Eibar v Las Palmas, Rayo Vallecano v Atletico Madrid
