Iniesta had a relapse on a thigh injury in the Champions League final while Pique will be out for 10-15 days with a muscle tear, according to the treble winners.
"We listen to everyone: the players, the coaches and the clubs," Del Bosque told a news conference after naming his 23-man squad. "Our medical team is capable of assessing any danger for the player, who is our primary concern.
"We'll take a view on Thursday when the squad joins up. I am confident they will all be ready for the tournament."
Villarreal's Santi Cazorla has just returned from almost two months out with a bone fracture and is also included.
Barcelona's Sergio Busquets comes in as a holding midfielder to replace the injured Marcos Senna, and another youngster, Valencia's Juan Mata, was included to give pace down the flanks.
"These three games concern me," Del Bosque said. "Our job is to make sure the players are fully focused for these games. Afterwards with semi-finals in front us the players would not need motivating."
