Luis Enrique's side have qualified for next year's European Championships with minimal trouble and are on course to reach the finals of the 2020-21 Nations League, with fixtures against Switzerland and Ukraine to come for Spain in the next eight days.
Owing to injuries and coronavirus-related concerns, Enrique has already been forced into a couple of squad alterations, and the Spain manager has several decisions to make when it comes to who will pull on the Spain jersey for the clash with Portugal.
Here, Sports Mole looks at how Spain could line up for the midweek showdown with their neighbouring nation.
As expected, Enrique has named a particularly strong contingent for October's fixtures, but a number of well-established internationals will be watching these matches from home.
Indeed, Saul, Koke, Isco and Alvaro Morata are among some of the big names to not be included in Enrique's squad, while Jordi Alba and Dani Carvajal are both sidelined through injury, although the former was not selected anyway.
Furthermore, Fabian Ruiz will not be involved either following the news of Napoli's coronavirus outbreak, and there is great competition for places in Spain's midfield for the midweek clash with Portugal.
Sergio Busquets could get the nod in front of the defence, while Dani Ceballos - on loan at Arsenal for a second season from Real Madrid - is in contention to start after earning a recall to the national side.
Owing to the absences of Alba and Carvajal, Tottenham Hotspur new boy Sergio Reguilon may be handed a start at left-back, while Sergi Roberto will be battling with Jesus Navas for the right-back spot, although we expect the Barcelona man to feature from the off.
Up top, Adama Traore was called up by both Spain and Mali, but the attacker was pictured reporting for duty with Enrique's squad and could be handed his international debut against Portugal, where he would face several of his Wolverhampton Wanderers teammates.
Leeds United's Rodrigo scored his first goal for his new club against Manchester City at the weekend and will look to lead the line, while 17-year-old Ansu Fati, who boasts three goals and one assist from three La Liga games this season, could complete the lineup.