Luis Enrique's side will be the overwhelming favourites to triumph on Friday night as they prepare to take on a side currently ranked outside of the top 100 teams in international football.
It will be just the third meeting between the two teams and Spain won the previous two with an aggregate score of 9-3.
Here, Sports Mole takes a look at how the 2010 world champions could line up.
Captain Sergio Ramos has not played a competitive game of football since the start of April, missing the latter stages of Real Madrid's 2018-19 campaign due to a hamstring problem. The centre-back is fit to feature for his country, though, and could once again be joined by Mario Hermoso at the heart of the defence.
David de Gea, Jordi Alba and Sergio Busquets were all left out against Malta last time out but should return, while Dani Parejo's excellent campaign for Valencia should earn the midfielder a spot in the XI.
Reported Manchester City target Rodri had a fine 2018-19 season with Atletico Madrid but could be named on the bench, with Isco potentially operating alongside Busquets and Parejo in a 4-3-3 formation.
Santi Cazorla's inclusion was the standout news when the Spain squad was announced. The Villarreal midfielder is back in the selection for the first time since November 2015 and will be desperate to be involved in some capacity.
Alvaro Morata's brace against Malta should be enough to see the 26-year-old start at the tip of the attack, meanwhile, and he could be joined by Rodrigo Moreno and Marco Asensio as part of a front three.