Real Madrid has been drawn against Africa-based Melilla in the Copa del Rey's round of 32, while Barcelona will also face third-tier opposition.
Holder Barca – which crushed Sevilla 5-0 in last season's final – gets its campaign started away to Cultural Leonesa, which was relegated from LaLiga2 last term.
Madrid's first-leg contest with Segunda B4 leader Melilla will see the side travel to one of Spain's two ports on the continent of Africa, though both – the other being Ceuta – are claimed by Morocco.
Arguably the standout draw for the smaller clubs left in the competition is that of fourth-tier side Sant Andreu, however, as it will play Atletico Madrid.
La Liga leader Sevilla is to face Villanovense, while Valencia was drawn with Ebro – two ties which should provide little difficulty for either of the top-tier clubs.
Sergio Canales will return to Racing Santander – the club he impressed for as a teenager – with Real Betis and there are four all-La Liga ties to look forward to, with Leganes and Rayo Vallecano set to go up against each other in a pair of Madrid derbies.
The first fixtures are provisionally due to take place on October 31, with the return games on December 5.