Vicente del Bosque has come under criticism for his decision not to field a recognised striker in the opening match against Italy, which left Spain without a focal point to channel their attacks.
It is likely the Spaniard will opt to play with a forward in the central role against Ireland, with Fernando Torres in line to be given the nod ahead of Alvaro Negredo and Fernando Llorente, despite missing two good chances to defeat the Azzurri after coming off the bench on Sunday.
Cesc Fabregas will make way for Torres in the starting XI, as the 25-year-old may not be fully fit after carrying a thigh injury into the tournament.
Sergio Ramos and Gerard Pique will continue their partnership in defence in the absence of Barcelona captain Carles Puyol, who misses the championship after knee surgery.
Ireland have some slight injury worries going into the match against the current European champions. Richard Dunne is suffering from blisters and fatigue after the 3-1 defeat to Croatia, although the central defender will play through the pain barrier to partner Sean St Ledger in defence.
Shay Given and Darron Gibson also missed training early in the week but head coach Giovanni Trapattoni has stated that the pair are fit and ready to play. Shane Long is also in contention to start.
James McClean may also feel aggrieved not to have featured against Croatia in the opening match, but Trapattoni has spoken of not putting too much immediate pressure on the 23-year-old in the tournament, so if he does play it will likely be as a substitute.
The last encounter between Spain and Ireland was in the 2002 World Cup. The last-16 match finished in a 1-1 draw, but the Spaniards managed to qualify for the next stage by winning 3-2 in the penalty shoot-out.
Spain`s draw with Italy in the opening match of Group C ended their run of 14 straight competitive victories, with their last defeat coming at the hands of Switzerland in the 2010 World Cup.
The reigning world and European champions have not missed a major finals tournament since the 1992 European Championship.
Vicente del Bosque`s side made 672 completed passes on matchday one, compared to Italy`s 341.
Ireland are making their first appearance in a European Championship finals since making their debut in the 1988 event in West Germany.
The Republic of Ireland had gone 14 matches unbeaten, since a 3-2 loss to Uruguay, before the reverse to Croatia on matchday one.
Aiden McGeady won his 50th cap against the Croatians; Kevin Doyle could reach his half-century versus Spain.
Sean St Ledger has scored three international goals for Ireland, including the header against Croatia. However, none of these goals resulted in a victory for the Irish.