Constanza Manuel of Villena (c. 1318 – 27 January 1349), was a Castilian noblewoman who by her two marriages was Queen consort of Castile and León and Infanta of Portugal.

Two years later, in 1327, Constanza was repudiated, as the Castilian monarch was more interested in marrying with his double first-cousin Infanta Maria of Portugal, daughter of King Afonso IV, in order to strengthen ties with the Lusitan kingdom.

[5] This agreement was not to the liking of the Castilian monarch who did everything possible to prevent Constanza from traveling to Portugal and imprisoned her at the Alcázar of Toro to pressure Don Juan Manuel to desist from this marriage.

[10] King Afonso IV complied with the agreement he had with Don Juan Manuel and he gave his daughter-in-law the arras that included the towns of Montemor-o-Novo and Alenquer as well as the city of Viseu as other Queens of Portugal previously received.

[15] As a way to end the affair of her husband and her relative, when Constanza gave birth her first son, Infante Luiz, she invited Inês to be his godmother.

According to the precepts of the Catholic Church at the time, the relationship between the godparent and a parent of the person being baptized was one of moral kinship, and their love would be almost incestuous;[16] however, the child would die within a week, which increased suspicions about Inês de Castro.

The adulterous romance would continue and intensified with time, until King Afonso IV exiled the Galician noblewoman to Alburquerque, on the Castilian border, in 1344.

[19] Constanza was initially buried in the Church of Santo Domingo in Santarém and later her son, King Fernando I, ordered that her tomb be transferred to the Monastery of San Francisco in the same city.