And while there will be plenty of changes as both sides rotate their troops, an entertaining match is still anticipated in Madrid.
Spain represent perhaps the biggest test of Jorge Sampaoli's tenure to date: can the Albiceleste coach take a memorable result just months from the start of the main event in June?
|Game||Spain vs Argentina|
|Date||Tuesday March 27|
|Time||20:30 BST / 15:30 ET|
TV Channel & Live Stream
In the United States (US), ESPN 3 will be screening the friendly live.
Viewers will also be able to watch a Spanish language transmission via ESPN Deportes +, while the game will be streamed via WatchESPN.
|US TV channel||Online stream|
|ESPN 3, ESPN Deportes +||WatchESPN|
In the United Kingdom (UK), the game can be watched live on Sky Sports Football and it can be streamed live online using Sky Go.
|UK TV channel||Online stream|
|Sky Sports Football||Sky Go|
Squads & Team News
|Goalkeepers||Reina, De Gea, Kepa|
|Defenders||Ramos, Pique, Azpilicueta, Jordi Alba, Nacho, Carvajal, M. Alonso, Odriozola|
|Midfielders||Iniesta, Koke, Thiago, Asensio, Saul, Rodri, Parejo|
|Forwards||Costa, Aspas, Rodrigo, Vazquez|
With David Silva unavailable, Spain coach Julen Lopetegui could turn to Saul to bolster his midfield.
Rodrigo, who netted against Germany, could also have another chance to shine up front, while Diego Costa is in line to start in front of his home crowd at the Wanda.
In defence Marcos Alonso may replace Jordi Alba, while Nacho is set to deputise for Gerard Pique, who is likely to be given a rest after his exertions in the first friendly.
Potential Spain XI: De Gea; Carvajal, Ramos, Nacho, Alonso; Iniesta, Koke, Saul, Asensio; Rodrigo, Costa.
|Goalkeepers||Caballero, Romero, Guzman|
|Defenders||Mercado, Tagliafico, Otamendi, Fazio, Funes Mori, Bustos, Rojo|
|Midfielders||Paredes, Biglia, Lo Celso, Banega, Mascherano, P. Perez, Acuna, Perotti, Lanzini, Meza|
|Forwards||Messi, Higuain, Martinez, Correa, Pavon|
Sampaoli has lost both Sergio Aguero and Angel Di Maria to injury, and Argentina have been dealt a blow with Messi's failure to return to fitness.
Having sat out Friday's 2-0 win over Italy, Messi has not recovered from an adductor niggle and is expected to miss the match in the Wanda Metropolitano.
Elsewhere the coach will shuffle his deck, with Javier Mascherano set to re-enter the starting line-up for his 142nd cap, equalling Javier Zanetti's Argentina record.
Probable Argentina XI: Romero; Bustos, Otamendi, Rojo, Tagliafico; Banega, Mascherano; Lo Celso, Lanzini, Meza; Higuain.
Betting & Match Odds
Spain are 21/20 favourites to win according to dabblebet, with Argentina priced at 5/2 to beat the Furia Roja. A draw is available at 9/4.
The pressure is on for both Spain and Argentina. Blessed with two of the most talented international squads in the game, expectations could not be higher for the upcoming World Cup.
The Roja are in the middle of a generational shift, having flopped so badly last time round in Brazil. New faces like Marco Asensio, Saul and Rodrigo are beginning to make their presence felt, as the stars that made 2010 glory possible begin to fade out of the picture.
Not entirely, though. Andres Iniesta showed on Friday that he remains among the world's elite midfielders, and with the likes of Gerard Pique and Sergio Ramos holding up the defence, Spain boast an enviable mix of youth and experience in their team which will be a match for any of the participating nations in Russia.
Looking to take the Roja down a peg in Madrid this Tuesday will be a team with perhaps more to prove than any other. Argentina have lost three consecutive finals, World Cup agony against Germany followed by consecutive Copa America defeats to Chile, and since Alejandro Sabella left his post in 2014 no less than three coaches have been hired by the Albiceleste in a bid for glory.
Now it is up to the audacious Sampaoli to deliver the goods, having led Argentina through the end of what was a tortuous qualifying campaign to make the finals. The ex-Chile and Sevilla man has had limited time to work with his new charges, but he is slowly beginning to impose a typically attacking, high-pressing style on a side that has had little continuity over the last four years.
Still, however, the nation remains heavily reliant on the talents of Messi. The Barcelona star was missed in a 2-0 win over Italy, and his absence will be felt again on Tuesday. Striker Gonzalo Higuain, meanwhile, will be watched closely after failing to hit the net at the Etihad Stadium, with young wonderkid Lautaro Martinez waiting patiently on the bench for his debut.
These friendlies represent a chance for Spain and Argentina to test out their squads, with competition absolutely fierce for each and every spot in the 23-man final lists. Much more than pride will be on the line in this clash between past World Cup winners, and no player will want to miss the chance to make a big impression on their coaches and seal their ticket to Russia.