In the third tier in Spain, Toni Aparicio's men surprisingly held Real to a 0-0 draw in the first leg of the last-32 tie at the Estadio La Murta.
Carlo Ancelotti had the likes of Angel Di Maria and Isco in his starting line-up for the clash but they failed to find a goal away from home and need to increase their intensity after a lacklustre week, which has included draws versus Olimpic and Osasuna.
A trip to the Santiago Bernabeu shapes as a daunting test for Olimpic, even if Real are again without superstars Cristiano Ronaldo and Gareth Bale.
The visitors will need plenty of luck and it would be a huge shock if Ancelotti's men, third in La Liga after a 2-2 draw against Osasuna on Saturday, failed to progress.
Elsewhere, Barcelona host Cartagena carrying a 4-1 lead from the first leg after surprisingly falling behind to the Segunda B side.
Gerardo Martino is likely to rest several of his regulars with such a big advantage heading to the Camp Nou.
Reigning champions Atletico Madrid should do the same as they prepare to welcome Sant Andreu after winning the opening leg 4-0.
Several other top-flight teams have work to do if they are to advance to the last 16.
Relegation-threatened La Liga side Real Betis lead Segunda B outfit Lleida Esportiu 2-1 ahead of a home clash.
Real Sociedad only claimed a 1-1 first-leg draw versus Algeciras, while Getafe host Girona after their match finished with the same scoreline.
Levante trail second-tier Recreativo Huelva 1-0, Valencia were held 0-0 by another Segunda B team in Gimnastic Tarragona and Espanyol host Real Jaen after their 2-2 draw.
An all-La Liga tie between Elche and Villarreal is locked at 2-2 ahead of a meeting at the Estadio Manuel Martinez Valero, while Real Vallecano and Real Valladolid drew their opener 0-0.
Sevilla lead Racing Santander 1-0 and Athletic Bilbao must overturn a 1-0 deficit when they host Celta de Vigo.
Granada welcome Alcorcon with a 2-0 advantage, Almeria host Las Palmas leading 3-1 and Osasuna and Malaga meet after a thrilling 3-3 draw first-up.
‘If I was Bournemouth, I’d be thinking if they can get past Manchester City, there’s no-one to stop them winning the FA Cup for the first time ever’ Former England star believes the Cherries have the ability to make history
‘I wasn’t concerned I’d done anything wrong – I stated a fact. It was taken out of proportion and people have recognised that they misread the situation a bit’ Gary Lineker gives FourFourTwo his thoughts on BBC suspension for asylum seeker tweet
