And Southgate, whose side reached the World Cup semi-finals in July, believes his players and teams across the league are paying the consequences of a lack of rest.
"I don't understand why our league started so early but it did and it's a really difficult situation for the clubs," Southgate said.
"Some couldn't field a team. Look at Tottenham, they had so many players in the semi-final and they had to put players straight into matches, it's an impossible situation for the coaches really."
Following the Nations League clash with Spain, England’s next game is friendly with the United States at Wembley Stadium on November 15.
England vs Spain TV: Find out why the match won't be on ITV (Image: GETTY)
England vs Spain TV: The Nations League match is being staged at the Benito Villamarin in Seville (Image: GETTY)
England team train ahead of Nations League clash
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In the UK, Sky Sports has been awarded the exclusive live rights to the inaugural UEFA Nations League.
The deal runs from 2018 to 2022 and includes the right to televise highlights of all matches during that period.
Sky Sports' package also includes the first two editions of the UEFA Nations League Final Four.
Free-to-air commercial broadcaster ITV has retained exclusive live rights to England's games in the European Qualifiers for Euro 2020 and the 2022 FIFA World Cup.
However, ITV will also be able to broadcast highlights of all England fixtures throughout the 2018–22 cycle, including Nations League fixtures.
England vs Spain TV: The Spaniards won the previous Nations League clash 2-1 (Image: GETTY)
Where can I watch England vs Spain tonight?
The Nations League will be shown on Sky Sports Main Event in the UK.
Pre-match coverage gets underway at 7pm ahead of kick-off at 7.45pm.
Existing Sky Sports customers will also be able to stream the match via the Sky Go app, which can be downloaded across a host of devices.
Fans without a Sky Sports subscription can still tune into the action through a NOW TV sports pass.
Day passes, which let you view Sky Sports channels for 24 hours, start at £7.99 a day, with a weekly pass starting from £12.99 and no locking in to a contract.