Gareth Bale scored a dramatic late winner as Carlo Ancelotti's men snatched a 2-1 victory over Barcelona in last season's final at the Mestalla - their 19th success in the competition.
Real, who have six players on the Ballon d'Or shortlist announced on Tuesday, head into the round-of-32 first-leg fixture on the back of a 3-0 win at Liverpool in the UEFA Champions League and a 3-1 El Clasico victory over Barca on Sunday.
It would be little surprise, then, to see Ancelotti rotate heavily for Wednesday's fixture, which has been brought forward due to Real's involvement in December's Club World Cup in Morocco.
Iker Casillas, Cristiano Ronaldo and Sergio Ramos are among those who could make way for the likes of Keylor Navas, Javier Hernandez and Raphael Varane at Estadi Cornella-El Prat - borrowed from Cornella's near neighbours Espanyol in a bid to maximise revenue from the glamour tie.
Near neighbours is no exaggeration, by the way - Cornella's Nou Camp Municipal sits in the shadow of their temporary home.
With Real set to ring the changes for the fixture, director of institutional relations and club legend Emilio Butragueno has warned against complacency.
"There have been a lot of surprises in the cup over the years and we will have to be very focused," he said when the draw was made earlier this month. "They [Cornella] are in mid-table in their division, but playing Real Madrid is always a great challenge and a huge motivation.
"They will be a dangerous opponent and we will very much have to be on our guard."
Cornella have made hard work of their progression to this stage, beating Jaen on penalties in round one before coming from behind to see off Zamora and Leioa.
And progression to the last 16 appears unlikely - even more so when you consider Real could be set for a meeting with city rivals Atletico Madrid should they progress.
If Real do defend their title this year, they will have earned it, as a potential clash with Barcelona awaits in the quarter-finals.
Sabadell will host Sevilla in the only other Cope del Rey fixture to be played before the rest of the ties begin in December.
