Gary Neville has a great chance to seal his first win as Valencia boss at the third attempt when Los Che host third tier Barakaldo at the Mestalla on Wednesday.

Valencia already lead the Basques 3-1 from the first leg before Neville's appointment a fortnight ago.

Real Madrid's expulsion from the competition for fielding an ineligible player against Cadiz could open the door for a winner outside Spanish football's dominant top three of Real, Barcelona and Atletico Madrid for the first time since 2010.

And Neville has targeted winning one of the Cup or the Europa League as one of his prime targets in his short stint at Valencia between now and the end of the season.

"Valencia have to win trophies," he told the club's website.

"The players have to experience the medal round their neck to give them confidence and belief."

Holders Barcelona have already assured their place in the last 16 with a 6-1 thrashing of Villanovense.

And, aside from Madrid's monumental error in fielding Russian international Denis Cheryshev when he was suspended due to an accumulation of yellow cards last season, there was little drama in the fourth round first legs as almost all of La Liga's big guns look on course to progress.

Atletico moved joint top of La Liga with an eighth consecutive victory in all competitions against Athletic Bilbao at the weekend and should make it nine when Reus visit the Vicente Calderon.

Diego Simeone's men hold a 2-1 advantage from the first leg despite naming a much changed side and a number of fringe players will get another chance to impress on Thursday.

Villarreal are one of the few top sides with work to do as they seek to overturn a 3-2 first leg deficit when they host second division Huesca fresh from beating Real Madrid.

La Liga strugglers Granada and Malaga trail Leganes and Mirandes 2-1 respectively.

And despite their great start to the league season, Eibar have an even more difficult task as they trail Ponferradina 3-0.

Meanwhile, last season's beaten finalists Athletic Bilbao, Sevilla, Celta Vigo and Deportivo la Coruna are all well set to progress as they hold comfortable leads against lower league opposition with the home leg to come.