The defending world and European champions won all four of their games in the previous international window including a 3-2 win over England at Wembley and a 3-1 home victory against the Czechs.
The hosts lost all four of their games, and Luis de la Fuente will be looking to extend La Roja's winning run, ahead of a rematch against England in Madrid on November 15.
Czechia v Spain team news
In a curious twist, the hosts will be led by a Spaniard, following Santi Denia's summer appointment. Experienced pair Vladimir Coufal and Tomas Soucek are in the squad, but Patrik Schick is a key absentee following his international retirement after the 2026 FIFA World Cup.
De la Fuente will be without key pair Lamine Yamal and Mikel Oyarzabal for this match - but they will be assessed again ahead of the England game. Barcelona duo Rodri and Dani Olmo are also out through injury, so De la Fuente will need to reshuffle his options in Prague.
Czechia v Spain predicted lineups
Czechia XI: Hornicek; Coufal, Krejci, Zima, Slama; Soucek, Kral, Cerv; Hlozek, Provod, Ambros.
Spain XI: Simon; Porro, Huijsen, Laporte, Cucurella; Pedri, Ruiz, Lopez; Munoz, Torres, Williams.
Czechia v Spain kick off time
Kick off in Prague is set for 8:45pm local time and 7:45pm in the UK.
Key stat
Since their first meeting during qualification for the 1998 World Cup in 1996, Spain are unbeaten in eight clashes with Czechia, and De la Fuente's team have not lost any games since June 2025.