Her regency was overshadowed by Spain's post-1648 decline and internal political divisions, combined with a general European economic crisis during the latter half of the 17th century.

[3] It has been suggested Charles inherited several rare genetic disorders from his parents, [4] but his elder sister did not experience the same issues, while the most significant study on this topic concludes such claims remain speculation.

[5] Regardless, Charles' death was expected almost from birth, leading to internal struggles between backers of his two potential co-heirs, Louis XIV and Emperor Leopold.

[6] Charles was only three years old when Philip died on 17 September 1665, and Mariana was appointed regent, advised by a Regency Council, until he became a legal adult at the age of 14.

[8] Charles' poor health and lack of an heir meant his reign was often dominated by a power struggle between Mariana's Austrian faction, and a pro-French lobby initially led by his illegitimate half-brother, John of Austria the Younger.

[15] In 1672, Spain was dragged into the Franco-Dutch War; Valenzuela was dismissed when Charles came of age in 1675, but Spanish policy continued to be undermined by the struggle for power.

John died in September 1679 and Mariana became regent once again; one of his final acts was arranging the marriage of Charles to 17-year-old Marie Louise of Orléans, which took place in November 1679.

[17] Her replacement was Maria Anna of Neuburg, one of 12 children whose family reputation for fertility made them popular choices for royal marriages.

[19] As his health declined, internal struggles over the succession became increasingly bitter, leadership of the pro-French faction passing to Fernández de Portocarrero, Archbishop of Toledo.