The Spanish sit comfortably atop Group A4 with six points and a plus seven goal difference after beating England and Croatia 2-1 and 6-0, respectively.
Meanwhile, the Three Lions picked up their first Nations League point in Croatia on Friday night in a goalless game played behind closed doors.
Gareth Southgate employed a 4-3-3 formation in that game, having utilised a 3-5-2 system for the entirety of the World Cup, and could be set to continue that experiment against Luis Enrique's side.
|Game||Spain vs England|
|Date||Monday, October 15|
|Time||7:45pm BST / 2:45pm EST|
TV Channel, Live Stream & How To Watch
In the United States (US), the game can be watched live and on-demand with fuboTV (7-day free trial) .
New users can sign up for a free seven-day trial of the live sports streaming service, which can be accessed via iOS, Android, Chromecast, Amazon Fire TV, Roku and Apple TV as well as on a web browser.
|US TV channel||Online stream|
|Univision Deportes/UniMas||fubo TV (7-day free trial)|
In the United Kingdom (UK), the game can be watched live on TV on Sky Sports Main Event and it can be streamed live online using Sky Go. The game can also be followed live on Goal here .
|UK TV channel||Online stream|
|Sky Sports Main Event||Sky Go|
Squads & Team News
|Goalkeepers||De Gea, Kepa, Lopez|
|Defenders||Azpilicueta, Jonny, Alonso, Gaya, Nacho, Ramos, Albiol, Bartra|
|Midfielders||Saul, Koke, Thiago, Rodri, Ceballos, Suso, Asensio, Busquets|
|Forwards||Alcacer, Aspas, Rodrigo, Morata|
Barcelona left-back Jordi Alba continues to be frozen out of the national team by his former club coach, with three left-backs named ahead of him in the squad.
Potential Spain XI: De Gea; Otto, Ramos, Nacho, Alonso; Busquets, Saul, Thiago; Asensio, Aspas, Rodrigo.
|Goalkeepers||Pickford, Butland, Bettinelli|
|Defenders||Chilwell, Stones, Maguire, Gomez, Dunk, Walker, Trippier, Alexander-Arnold|
|Midfielders||Dier, Winks, Maddison, Mount, Chalobah, Barkley|
|Forwards||Kane, Welbeck, Rashford, Sancho, Sterling|
Goalkeeper Alex McCarthy and left-back Danny Rose were both forced to withdraw from the squad ahead of the Croatia game due to injury concerns, meaning that Southgate is notably light on left-back options outside of Leicester City's Ben Chilwell, with Luke Shaw also sidelined.
Several young players will be hoping for their full debuts against Spain, with the likes of Jadon Sancho, James Maddison and Mason Mount called up to the senior squad for the first time, with Dele Alli and Jesse Lingard absent through injury.
Jordan Henderson is suspended after his yellow card against Croatia, with Harry Winks stepping in as his replacement.
Potential England XI: Pickford; Trippier, Gomez, Maguire, Chilwell; Dier, Winks, Barkley; Rashford, Kane, Sterling.
Betting & Match Odds
Spain are favourites to win the match according to bet365 , who price them at 3/5. England are considered a 9/2 bet to win away from home and a draw is available at 29/10.
England were beaten 2-1 by Spain at Wembley in September's maiden round of Nations League fixtures.
Marcus Rashford's 11th-minute opener was swiftly cancelled out by Saul Niguez, before a Rodrigo goal just after the half-hour mark proved decisive.
The Three Lions will be hoping for better this time around, as any result for Spain effectively clinches them top spot in the group, and leaves England and Croatia battling each other to avoid relegation.
And La Roja have been in fine form of late, dismantling Wales 4-1 in their recent friendly despite their injuries and with a handful of key names rested.
England, however, have laboured since exiting the World Cup and losing the third-place playoff, with their only win since then coming in narrow 1-0 victory over Switzerland at home.
Both squads are much-changed since the showpiece event in Russia, and both are missing key players, but Luis Enrique's men will perhaps feel confident of a result at home against an inexperienced English midfield.