The two sides played out a 1-1 draw when they met in Turin last year, with Daniele De Rossi coming to the Azzurri's rescue as the Roma midfielder's late penalty cancelled out Vitolo's opener.
Both teams are unbeaten and boast an identical points haul after six games - with Spain leading through goal difference - so Saturday's meeting in Madrid presents a chance for one of them to pull clear at the top.
|Game||Spain vs Italy|
|Date||Saturday, September 2|
|Time||19:45 BST / 14:45 ET|
TV CHANNEL & LIVE STREAM
In the UK, the match will be available to watch live on television on ITV 4 and by online stream using the ITV Player or app.
|UK TV channel||Online stream|
|ITV 4||ITV Player|
In the US, the match will be available watch live on television on FS2 as well as being available to stream live online using Fox Sports GO.
|US TV channel||Online stream|
|FS2||Fox Sports GO|
SQUADS & TEAM NEWS
|Goalkeepers||De Gea, Arrizabalaga, Reina|
|Defenders||Ramos, Azpilicueta, Pique, Bartra, Carvajal, Nacho, Monreal, Alba|
|Midfielders||Busquests, Iniesta, Koke, Thiago, Asensio, Silva, Isco, Niguez, Suso|
|Forwards||Villa, Morata, Pedro, Deulofeu, Aspas, Vazquez|
Spain's record goalscorer David Villa has returned to the national team at the age of 35 and could be set to feature for his country for the first time since the 2014 World Cup.
Potential starting XI: De Gea; Carvajal, Pique, Ramos, Alba; Busquets, Iniesta, Silva, Asensio, Isco; Morata.
|Goalkeepers||Buffon, Donnarumma, Perin|
|Defenders||Conti, Darmian, Spinazzola, Astori, Barzagli, Bonucci, D'Ambrosio, Rugani|
|Midfielders||Pellegrini, Candreva, Verratti, Insigne, De Rossi, Montolivo, Bernardeschi, El Shaarawy, Parolo|
|Forwards||Belotti, Immobile, Eder, Gabbiadini|
Giorgio Chiellini was named in the initial squad, but the Juventus defender has been forced to withdraw after suffering a calf injury.
Potential starting XI: Buffon; Barzagli, Bonucci, Darmian, Conti; De Rossi, Pellegrini, Verratti; Immobile, Insigne, Belotti.
BETTING & MATCH ODDS
Spain are considered favourites at odds of 5/6 according to dabblebet, with Italy priced at 15/4 to win in Madrid. A draw, which was the result when the teams met in Turin last October, is available at 12/5.
Alvaro Morata is the favourite to open the scoring at 15/4 with Italy duo Andrea Belotti and Ciro Immobile both priced at 13/2 to score first. David Villa, meanwhile, is 5/1 to score the first goal and 7/4 to score any time during the game.
Spain and Italy are locked level on points at the top of Group G and both sides will be eager to take advantage in the race for World Cup qualification when they take to the field in the Spanish capital.
However, if their previous meeting at Juventus Stadium is any indication of what is to come on Saturday, there will be plenty of caution applied to proceedings.
Theoretically, the hosts will be able to invest much more into the game, with a relatively less difficult encounter with Liechtenstein coming three days later, while Italy must prepare for a potentially tricky tie against Israel.
Indeed, the visitors' task has been made somewhat more difficult following the loss of key defender Chiellini to injury.
Nevertheless, with the prize of automatic qualification likely to go to the victor of this game and both sides possessing an array of quality within their ranks, it is sure to be an engaging battle.