La Roja are the overwhelming favourites to top a section which also includes the Faroe Islands, Malta, Norway, Romania and Sweden, and they will be confident of collecting all three points in this weekend's affair.
A mixed UEFA Nations League campaign last year saw Spain win two and lose two of their four matches; they started with impressive back-to-back victories away to England and at home to Croatia, before losing both of the reverse fixtures to ultimately finish second in the section behind the Three Lions.
There is no getting away from the fact that it has been a disappointing few years for Spain; they exited the 2014 World Cup in the group stage before being knocked out of last year's World Cup in the round of 16. The likes of Andres Iniesta, David Silva and Gerard Pique can no longer be called upon, which would hurt any side.
La Roja are three-time winners of the European Championships - including back-to-back titles in 2008 and 2012 - but they were eliminated from the 2016 competition in the round of 16. It has been a period of underachievement, but Luis Enrique's side must feel that they can challenge for Euro 2020, if they indeed make the finals.
This is Spain's first international of 2019; they beat Bosnia-Herzegovina in the latter stages of 2018, but it was far from a convincing performance, with Brais Mendez scoring the only goal of the match in the 78th minute.
There is still plenty of experience in the squad in the shape of Sergio Ramos, Jordi Alba, Sergio Busquets and Jesus Navas, but Sergi Gomez, Sergio Canales and Jaime Mata will all be looking to win their first caps in the upcoming games against Norway and Malta.
There will be a slight concern about Spain's attack, however, as Ramos is the leading scorer in the squad with 17 goals. Alvaro Morata is next in line with 13, but Rodrigo only has four, while Marco Asensio and Iker Muniain have just one international strike between them.
There have been stronger Spain squads, and if the European nation are to challenge for the 2020 title then the likes of Asensio - disappointing for Real Madrid this season - will really need to step forward.
Enrique's side should be able to get off to a positive start in this particular campaign, though, as they host Norway on Saturday before travelling to Malta for their second match on Tuesday night.
Recent form (all competitions): WWWLLW
Norway have not qualified for the finals of a major competition since Euro 2000, which proved to be the first ever time that they had made the finals of the European Championships, which does seem incredible.
They actually won eight of their 10 qualification matches en route to Euro 2020 but did not make it past the group stages in the actual competition, winning just one of their three matches.
Norway have not qualified for the finals of a World Cup since France 1998, meanwhile, sitting out each of the last five tournaments. For a team with a lot of talented players, that is simply not a good enough record.
Lars Lagerback's side had a strong UEFA Nations League campaign, however, winning four of their six matches to finish top of Group 3 of League C. As a result, they will bring a four-game unbeaten run into this match, having overcome Slovenia, Bulgaria and Cyprus since their last loss - a 1-0 reverse to Bulgaria.
It is a tough ask to expect Norway to triumph on Saturday night, but they have a huge game at home to Sweden next week before hosting Romania in their third match in the section on June 7.
There is a lot of talent and indeed experience in the Norwegian squad, with Fulham's Havard Nordtveit, Celtic's Kristoffer Ajer, West Bromwich Albion's Stefan Johansen, Southampton's Mohamed Elyounoussi and Bournemouth's Joshua King among those selected.
Unlike Spain, meanwhile, Norway have a core of forwards with a decent scoring record at international level; King has 12 in 37 caps, Ola Kamara has six in 13, while Tarik Elyounoussi, Alexander Sorloth and Bjorn Johnsen have 13 between them.
The Lions are the huge underdogs ahead of Saturday's clash in Valencia, but this is not the Spain of previous years and Lagerback's side will be eyeing a shock result at the Mestalla.
Recent form: WLWWDW
The likes of Real Madrid's Isco and Atletico Madrid pair Saul Niguez and Koke were not included in the latest Spain squad, while Isco's club teammate Dani Carvajal is currently on the sidelines through injury.
As a result, a number of players will be given opportunities; the back four almost picks itself with Inigo Martinez starting alongside the skipper Ramos, while Dani Ceballos and Dani Parejo could join Busquets in midfield.
Morata is expected to lead the line, meanwhile, with Muniain and Rodrigo also in line for starts. Asensio is another option for Enrique, but the attacker has struggled for form at club level this season.
Napoli's Fabian Ruiz had been included in the squad for the first time, but the 22-year-old was forced to withdraw after coming down with an illness ahead of this weekend's clash.
As for Norway, Celtic's Ajer has been given the all-clear to play following a head injury and should start.
There is also expected to be a spot in attack for Bournemouth forward King, who has scored 11 Premier League goals for the Cherries during the 2018-19 campaign.
Spain possible starting lineup:
De Gea; Roberto, Ramos, Inigo, Alba; Busquets, Parejo, Ceballos; Muniain, Morata, Rodrigo
Norway possible starting lineup:
Jarstein; Elabdellaoui, Nordtveit, Ajer, Rosted; Fossum, Henriksen, Selnaes, Elyounoussi; Kamara, King
Head To Head
Saturday will be just the seventh international meeting between the two nations.
Spain have won four of the previous six, suffering just one defeat, which came at Euro 2020.
Their last two meetings came in the playoffs ahead of Euro 2004 and Spain ran out 5-1 winners on aggregate, which included a 2-1 home success in November 2003.
We say: Spain 2-0 Norway
This could be a tricky game for Spain, who have a very different look. Enrique's side should have enough, though, to open their qualification campaign with a win.