Holders Sevilla will look to continue their recent revival when they welcome Barcelona to the Ramon-Sanchez Pizjuan on Wednesday in the first leg of their Copa del Rey last 16 tie.
Manolo Jimenez's side have won five and drawn two of their last seven competitive games - having previously lost three in five - and at the weekend thumped local rivals Real Betis 3-0.
Their clash with Barcelona is undoubtedly the pick of the last 16 matches, and one that both clubs will be especially desperate to win considering Real Madrid appear to be storming away with the league.
'It is a big match and we are in the form to be able to have a great game and beat Barcelona, why not?' said Sevilla striker Luis Fabiano, whose brace against Betis at the weekend took him to a league-leading 12 goals for the season.
'Playing like we did on Sunday we have a great chance to beat them.'
Barcelona defender Rafael Marquez, who was also on the scoresheet at the weekend after netting the opener in a 2-0 win at Real Mallorca, is anticipating a tough night on their trip to Andalusia.
'Sevilla are a very strong opponent, who recently have been playing very well,' the Mexico international said.
'We would have preferred another opponent at this stage of the competition but we have to go and give everything to win and get through to the next round.'
The African Nations Cup means both teams will be missing key players, with Sevilla losing Fredi Kanoute, Arouna Kone and Seydou Keita, and Barcelona having to do without Yaya Toure.
However, Barca striker Samuel Eto'o is available for Frank Rijkaard's side as he will not join up with Cameroon until next week.
Valencia also travel to Seville on Wednesday as they take on Real Betis, and they have named new signing Ever Banega in an 18-man squad for the game.
The 19-year-old midfielder recently moved from Boca Juniors and took part in his first training session with Los Che on Monday morning.
'He is a player who can contribute good things, and above all he has come here with the desire to play as soon as possible,' said Valencia winger Joaquin, who is looking forward to the game against his former club Betis.
'It is emotional because of my past with Betis. It is a special game because it is the cup and we have a lot of hope in this competition.'
In other matches, last season's runners-up Getafe will look to bounce back from a 3-0 home defeat to Real Valladolid at the weekend when they host La Liga's bottom club Levante, while Valladolid are back in Madrid to take on Atletico.
Athletic Bilbao welcome in-form Espanyol, who are unbeaten in 16 league and cup matches, while Recreativo Huelva play host to Villarreal and Racing Santander go to Real Zaragoza.
Spanish champions Real Madrid, who were somewhat fortunate to beat Real Zaragoza 2-0 on Sunday to maintain their seven-point lead at the Primera Liga summit, are away to Real Mallorca in the first leg of their last 16 tie.
The return legs are scheduled to take place on January 16.