Isabel was born in Seville around 1329, she was the youngest of three surviving children; her elder brothers were Luis and Juan de la Cerda y Guzmán, she had five other siblings who died in childhood.
[3] A charter dated 30 December 1353 records the agreement between Isabel and her two brothers over their father's estate,[4] who had died in 1348.
Isabel remained unmarried for up to fourteen years, she then remarried at Seville on 15 September 1370 to Bernal de Foix, an illegitimate son of Gaston III, Count of Foix .
As Isabel had a strong claim on the Castillian throne, on 25 May 1366 she was granted large estates by Henry II of Castile on the condition that she relinquish all claim to the Crown of Castile for herself and her heirs.
[5] The Medinaceli dukes had extensive estates in the Spanish provinces of Soria and Guadalajara.