The Reina Sofía collection has works by artists such as: Juan Gris, Joan Miró, Julio González, Eduardo Chillida, Antoni Tàpies, Pablo Gargallo, Pablo Serrano, Lucio Muñoz, Luis Gordillo, Jorge Oteiza and José Gutiérrez Solana.
Zagotovo najbolj znana mojstrovina v muzeju je Picassova sliko Guernica.