Luis de la Fuente's team showed real resilience at Wembley as they battled back to open up their UEFA Nations League campaign with a 3-2 win over England.
Croatia also needed to dig deep in their first match of the series, winning 2-1 in Czechia, and this clash has all the ingredients for a real battle in Andalucia.
Spain v Croatia team news
De la Fuente has a star-studded squad at his disposal and he could freshen things up after a marathon night in London.
The hosts defence could be unchanged, but Barcelona playmaker Pedri should rotate back into the engine room, and Mikel Oyarzabal may start over Ferran Torres in attack.
Luka Modric will captain Croatia with former LaLiga star Ante Budimir ready to lead the attack.
Spain v Croatia predicted lineups
Spain XI: Simon, Pubill, Cubarsi, Laporte, Cucurella; Pedri, Rodri, Ruiz; Lamine Yamal, Oyarzabal, Nico Williams.
Croatia XI: Livakovic; Stanisic, Gvardiol, Vuskovic, Perisic; Modric, Kovacic, Vlasic; Sucic, Budimir, Kramaric.
Spain v Croatia kick off time
Kick off at the Estadio Ramon Sanchez Pizjuan is set for 8:45pm local time and 7:45pm in the UK.
Key stat
Spain have faced Croatia in back-to-back European Championships - and won both games - with an overall unban run of three games against them.