Former Manchester United defender Pique, 22, and 20-year-old midfielder Busquets are part of a five-strong contingent from the Primera Liga leaders, alongside regulars Xavi, Carles Puyol and the fit-again Andres Iniesta.
"We have to take the team forward step by step and plan for the future," Del Bosque said at a news conference.
The inclusion of Pique and Busquets was part of a final chance for the European Champions to experiment before the World Cup qualifier against Turkey on March 28, the former Real Madrid coach added.
Iniesta missed the 3-0 friendly win over Chile in November after picking up a thigh problem. Valencia forward David Silva also returns to the squad after an injury layoff.
Del Bosque kept faith with Athletic Bilbao striker Fernando Llorente, who won his first cap against Chile and has been in fine goal-scoring form in recent weeks.
Llorente, 23, will compete for a place in the starting lineup with Fernando Torres, David Villa and Daniel Guiza.
"It's good that we have quite a bit of competition up front," Del Bosque said.
Torres is one of five Liverpool players in the squad together with number two goalkeeper Pepe Reina, defender Alvaro Arbeloa and midfielders Xabi Alonso and Albert Riera.
Squad:
Goalkeepers: Iker Casillas (Real Madrid), Pepe Reina (Liverpool).
Defenders: Raul Albiol (Valencia), Alvaro Arbeloa (Liverpool), Joan Capdevila (Villarreal), Juanito (Real Betis), Carlos Marchena (Valencia), Carles Puyol (Barcelona), Sergio Ramos (Real Madrid), Gerard Pique (Barcelona).
Midfielders: David Silva (Valencia), Xabi Alonso (Liverpool), Santi Cazorla (Villarreal), Sergio Busquets (Barcelona), Xavi (Barcelona), Andres Iniesta (Barcelona), Albert Riera (Liverpool), Marcos Senna (Villarreal).
Forwards: David Villa (Valencia), Daniel Guiza (Fenerbahce), Fernando Torres (Liverpool), Fernando Llorente (Athletic Bilbao).
