Political career
From that day Serrano became one of the chief military politicians of Spain. In 1841, he helped Espartero to overthrow the regency of Maria Christina of Bourbon-Sicily. In 1843, at Barcelona he made a pronunciamiento against Espartero. He was appointed as the minister of war in the cabinet of Joaquín María López y López, which convoked the Cortes that declared Queen Isabella of age at thirteen. He served in the same capacity in an Olozaga cabinet, sulked as long as the Moderates (Moderados) were in office.
In 1845, he was appointed as a senator, and in 1848 as captain-general of Granada. From 1846 to 1853, he was away from politics, living on his Andalusian estates or traveling abroad.
On 29 September 1850 in Madrid, Serrano married his first cousin, Antonia Domínguez y Borrell, Guevara y Lemus, 2nd Countess of San Antonio, with whom he had five children.
Serrano assisted Marshal Leopoldo O'Donnell in the military movements of 1854 and 1856, and was his staunch follower for twelve years.