Luis Enrique's side are currently top of the section with four points to show from their two previous games, while Switzerland sit bottom with just one point from their two fixtures thus far.
Spain started their UEFA Nations League campaign with a 1-1 draw against Germany at the start of September before recording a 4-0 win over Ukraine three days later, which has left them top of the section.
Enrique's side were in action on Wednesday night, meanwhile, drawing 0-0 with Portugal in an international friendly, with the match acting as valuable preparation for their next two fixtures.
It would be fair to say that Spain have had their problems in recent years, but they breezed through their qualification section for next summer's European Championships, winning nine of their 10 matches.
La Roja also now unbeaten in all competitions since losing to Croatia in the 2018-19 edition of this particular tournament, a run which stretches 14 matches.
The 2010 world champions will be determined to put another three points on the board here ahead of their fourth game in the section away to Ukraine on October 13.
Switzerland, meanwhile, started their 2020-21 UEFA Nations League campaign with a 2-1 defeat against Ukraine on September 3 before picking up a point in a 1-1 draw with Germany three days later.
Vladimir Petkovic's side are bottom of Group 4 with one point, but there is no question that they will have been encouraged by their performance against Germany last time out.
Switzerland will enter the match off the back of a 2-1 defeat to Croatia in a friendly on Wednesday, though, and now face successive away games against Spain and Germany.
Nati impressed in the 2018-19 version of the UEFA Nations League, topping a group that included Belgium before losing to eventual winners Portugal in the semi-finals of the competition; Petkovic's side were then beaten by England on penalties in the third-place playoff after a goalless draw.
Spain Nations League form: WWLLDW
Spain form (all competitions): DWWDWD
Switzerland Nations League form: WWLLLD
Switzerland form (all competitions): WWWLDL
A 4-3-3 formation could include both Sergio Busquets and Rodri in the middle of the park, while Gerard Moreno could again get the nod through the middle with Dani Olmo and Fati operating in the wide positions.
Sergio Canales and Dani Ceballos both started against Portugal but could now drop out, while there is no Fabian Ruiz for La Roja as the Napoli midfielder has been unable to travel to Spain due to quarantine rules after a coronavirus outbreak at his Italian club.
Liverpool's Xherdan Shaqiri was expected to miss out after recently testing positive for coronavirus, but the attacker has now returned a negative result and will travel to Spain.
Manuel Akanji, though, is currently in isolation and will therefore not be involved.
Spain possible starting lineup:
De Gea; Navas, Ramos, Torres, Gaya; Merino, Busquets, Rodri; Fati, Moreno, Olmo
Switzerland possible starting lineup:
Sommer; Widmer, Elvedi, Comert, Rodriguez, Benito; Zuber, Sow, Xhaka, Freuler; Seferovic
We say: Spain 2-1 Switzerland
Switzerland are certainly capable of making it a very uncomfortable evening for Spain, who are still feeling their way into a new era. We are expecting a very tight game on Friday evening but believe that the hosts will just have enough quality to pick up all three points in the Spanish capital.