Isabella's father played a crucial role as regent for her cousin, Afonso V, during his minority. It was during this period that Isabella and Afonso formed a deep bond, eventually falling in love with each other. Their engagement in 1445, however, triggered a conflict between Isabella's father and Duke Afonso of Braganza, who had hoped for the king to marry his own grandchild. Despite the opposition, Isabella and Afonso were united in matrimony on May 6, 1447, when they were both just fifteen years old.

The early years of their marriage were marked by political dynamics and shifting alliances. In 1448, King Afonso V appointed Afonso of Braganza as his advisor, leading to the death of Isabella's father and the exile of her brother, John. Despite these tumultuous events, Isabella remained in the king's favor, assuming control over the duchy of Coimbra until her brother's return to Portugal in 1454.

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Tragedy struck in 1455 when Queen Isabella passed away at the young age of twenty-three. The cause of her death remains a subject of speculation, with some suggesting poisoning as a possibility. Nevertheless, Isabella's legacy endured through her three children: John, Prince of Portugal, Joan, Princess of Portugal (later known as Saint Joan of Portugal or Saint Joan Princess), and John II of Portugal, who succeeded his father as the 13th King of Portugal.

Isabella's impact extended beyond her immediate family. She honored her father with a grand ceremony of exoneration at court and oversaw his reburial in a manner befitting his position. Her devotion to her family and her sense of duty as queen left an indelible mark on Portuguese history.

Queen Isabella's life encapsulates the complexities of royal alliances, political intrigues, and personal tragedies. Her story is a testament to the challenges faced by noblewomen during the tumultuous times of the 15th century. Despite her untimely demise, Isabella's influence continues to resonate, shaping the course of Portuguese history and leaving a lasting legacy for future generations to admire.