La Roja currently sit one point clear of Portugal at the top of the standings, while their visitors are at risk of being relegated to League B with defeat.
Match preview
The current Spain crop may no longer strike fear into the hearts of teams with the same ferocity as in 2010, but Luis Enrique's side can still be considered as genuine World Cup contenders by some ahead of the journey to Qatar.
La Roja have been paired with Costa Rica, Japan and Germany in Group E and also have the chance to seal first place in their Nations League group this week, as they aim to go one better than last year's defeat to France in the showpiece event.
Enrique's men have taken eight points from a possible 12 to open up a one-point gap over second-placed Portugal - whom they will meet on matchday six - as goals from Carlos Soler and Pablo Sarabia propelled them to a 2-0 win over the Czech Republic in their most recent game.
Should Spain get the better of Switzerland and the Czech Republic claim a surprise win over Portugal this weekend, Enrique's side will seal their place in the Nations League finals, but it could all come down to the clash of the Iberian giants next week.
An eight-game unbeaten run in all competitions stands Spain in good stead before the visit of Switzerland, and not since October 2018 have La Roja suffered defeat of any sort on home soil, although that was in the inaugural Nations League against England.
Spain fans will be rooting against Switzerland on Saturday, but La Roja would have undoubtedly been cheering the basement side on during their matchday four clash with Portugal, as they upset the apple cart to run out 1-0 winners in Geneva.
Haris Seferovic took just 57 seconds to head home the game's only goal and keep Switzerland's hopes of survival in League A alive, but a first-ever relegation to League B is still a real possibility for Murat Yakin's side, who lost their first three games of the 2022-23 Nations League.
The gap to third-placed Czech Republic is only standing at one point, meaning that the Swiss could usurp their League A rivals with victory in Zaragoza, but their relegation could also be sealed with defeat if Jaroslav Silhavy's side overcome Portugal.
Cameroon, Brazil and Serbia will await Switzerland in a challenging World Cup group later this year, so facing opponents of such high calibre in the Nations League will only benefit the Rossocrociati's chances of holding their own in Qatar, but they travel to Spain having lost each of their last three away games in all competitions.
Pablo Sarabia scored the only goal as Spain ran out 1-0 winners over Switzerland when the sides met in June, and the Rossocrociati have only ever won one of their 24 previous clashes with La Roja, which came in the group stage of the 2010 World Cup.
Spain form (all competitions):
W
W
D
D
W
W
Switzerland form (all competitions):
L
D
L
L
L
W
Team News
Spain are working with a number of notable absentees for September's fixtures, as Aymeric Laporte and Mikel Oyarzabal miss out due to injury, while Ansu Fati and Thiago Alcantara have also been left at home amid their fitness struggles this season.
David de Gea and Sergio Ramos will not represent their country this month either, but there is room for two uncapped strikers in Borja Iglesias and Nico Williams, both of whom will be looking to ease the burden on incumbent number nine Alvaro Morata.
Unai Simon will retain possession of the gloves in De Gea's absence, while Jordi Alba has also been called up despite losing his place in the Barcelona team to teenager Alejandro Balde and will expect to start at left-back.
As far as Switzerland are concerned, Red Bull Salzburg striker Noah Okafor is not involved this month due to reported dental issues, so 25-goal striker Seferovic is sure to lead the line, potentially with Breel Embolo and Xherdan Shaqiri in support.
The visitors are also sweating over the fitness of Ricardo Rodriguez, who missed Torino's most recent Serie A game due to a fever, and the 30-year-old needs just two more caps to reach 100 for his country.
Kevin Mbabu could be forced to fill in at left-back if Rodriguez is not passed fit, but the latter will have had ample time to recover from his illness and could form part of an unchanged Swiss XI.
Spain possible starting lineup:
Simon; Carvajal, Garcia, Torres, Alba; Gavi, Busquets, Koke; Sarabia, Morata, Torres
Switzerland possible starting lineup:
Omlin; Widmer, Akanji, Elvedi, Rodriguez; Freuler, Xhaka, Sow; Shaqiri, Seferovic, Embolo
We say: Spain 2-0 Switzerland
History ought to repeat itself for Switzerland this week, as the Rossocrociati have notably struggled for results against Spain in decades gone by, and their recent spate of losses on the road will do them no favours here either.