He later moved to Spain, following his cousin Francesco Maria II Pico della Mirandola,[2] and resided in Madrid at the Spanish Court for the rest of his life, where he held various offices and obtained various prebands and honours,[3] including the archdeaconry of Cordoba, which he was given on 25 October 1743.

[4] On 3 November 1744, he was appointed Courtier of the King of Spain, with the mission of accompanying the infanta María Teresa Rafaela, together with the Duchess of Mirandola, to the French border.

[4] After the death of Francesco Maria Pico della Mirandola (26 November 1747), having remained the last male descendant of the Pico della Mirandola family, he secretly married in 1748 Margherita Eleonora Pio di Savoia y Spinola (1720–1796), daughter of Francisco Pío de Saboya y Moura, Prince of San Gregorio, Duke of Nochera and Marquis of Castel Rodrigo, and of Giovanna Spinola y La Cerda, of the Dukes of the Sesto;[5] no children were born of the marriage.

[4] The couple commissioned the architect Francisco Sánchez to build the palace of Villahermosa (now housing the Thyssen-Bornemisza Museum), whose façade reflected the complex personality of the Abbot Pico, with a mixture of Italian, French and Spanish architectural elements and an elegance unusual for Madrid at the time.

His opera Il vellocino d'oro (translated into Spanish as El vellón de oro) was first performed at the Buen Retiro Palace in 1749 with music by Giovanni Battista Mele, and was rewarded with 13,000 reales, as well as a gold case decorated with brilliants and two barrels of tobacco; the serenade Le Mode (in Spanish Las Modas) was performed in 1754, with music by Nicola Conforto, at the Royal Palace of Aranjuez and was rewarded with a ring adorned with a round brilliant.