Asier Illarramendi makes his Spain debut and Iago Aspas starts up front against a strong Colombia side, which includes James Rodriguez.
Illarramendi has been rewarded for a consistent 2016-17 campaign with Real Sociedad, playing in the deep-lying, midfield role usually occupied by Sergio Busquets.
Elsewhere, Dani Carvajal and Sergio Ramos are rested from their Champions League exploits with Real Madrid and replaced by Cesar Azpilicueta and clubmate Nacho Fernandez, who did not feature in Cardiff.
Aspas is also given his first international start, ahead of Alvaro Morata and Diego Costa.
Colombia, meanwhile, are at full strength, with James named as their No 10, behind former Atletico Madrid star Radamel Falcao.
Ajax defender Davinson Sanchez, reportedly courted by Barcelona, joins the pair in the Tricolor’s XI.
Spain: Reina; Azpilicueta, Pique, Nacho, Alba; Illarramendi, Koke, Iniesta; Silva, Aspas, Pedro
Subs: Kepa, De Gea, Ramos, Carvajal, Monreal, Sergi Roberto, Busquets, Thiago, Isco, Asensio, Vitolo, Morata, Deulofeu, Costa
Colombia: Ospina; Arias, Davinson, Zapata, Armero; Aguilar, Carlos Sanchez; Cuadrado, James, Cardona; Falcao
Subs: Oscar Murillo, Barros, Bacca, Vargas, Yerry, Muriel, Medina, Daniel Torres, Fabra, Gutierrez, Moreno, Borja, Izquierdo
Referee: Vinicic (SVN)