Barcelona will face Athletic Bilbao in the last 16 of the Copa del Rey in a repeat of the 2009 final, while Valencia face rivals Villarreal.
Those two ties were the pick of Thursday's draw, which was not only for the last 16 of the competition but also for the quarter-finals and semi-finals.
Barca and Athletic are the two most successful sides in the competition's history and the Catalan giants extended their record to 25 triumphs with a 4-1 win over the Basque outfit (23 cups) last year - one of a record-breaking six trophies won by Pep Guardiola's men in 2009.
The winner of that match will face either second division pacesetters Real Betis or Getafe in the last eight.
If Barca go all the way to the final, then they could meet arch-rivals Real Madrid after the two Spanish giants fell in opposite halves of the draw.
Madrid, who won the last of their 17 cup crowns back in 1993, were rewarded for progressing beyond the last 32 for the first time in three years with a clash against Primera Division strugglers Levante.
Madrid had suffered embarrassing exits at the hands of Segunda Division B sides Real Union and Alcorcon in the last two seasons but, with Jose Mourinho now at the reins, they cruised past another third-tier side with a 5-1 aggregate win over Real Murcia.
If Madrid get past Levante - who they were held to a 0-0 draw by away from home in La Liga in September - then they could come up against neighbours Atletico in the next round.
Atletico, runners-up to Sevilla in last season's competition, next meet 2006 winners Espanyol.
In a repeat of this weekend's league fixture, east coast neighbours Valencia and Villarreal do battle against each other in their last-16 tie.
Awaiting them in the quarter-finals will be either holders Sevilla or a Malaga side who are now under the guidance of former Madrid and Villarreal coach Manuel Pellegrini.
In the two other ties, Almeria take on Real Mallorca and Segunda Division Cordoba - one of only two non-Primera Division sides left along with Betis - face Deportivo La Coruna.
The last-16 matches are scheduled to be played on December 22 and January 5.
