In July 1576, the Medici family’s hunting lodge outside Florence became the scene of a murder that shocked even a court accustomed to violence. Isabella de’ Medici, daughter of the first Grand Duke of Tuscany, was strangled to death by her own husband, Paolo Giordano Orsini, with the tacit approval of her brother, the ruling Grand Duke Francesco. She was 33 years old. Six days earlier, her sister-in-law Eleonora di Toledo had been strangled by her own husband, Pietro de’ Medici, using a dog leash.

The two deaths were the brutal culmination of a pattern of family control that had shaped the lives of every Medici daughter—and had already claimed nearly all of them before they reached middle age. The story of those daughters begins with their father, Cosimo de’ Medici. Born in 1519 and raised on the rural family estates of the Mugello Valley, Cosimo belonged to a dynasty that had clawed its way back to power after being expelled from Florence in 1494. Through wealth, banking, and patronage, the Medici had once ruled the republic from behind the scenes, and in the early 1510s they reclaimed their position amid the shifting politics of the Italian Wars.
In 1530, Cosimo’s cousin Alessandro was installed as the first Duke of Florence, transforming the republic into a hereditary state. Cosimo, a member of a junior line of the family, expected to live quietly in the country. That changed in 1537, when Alessandro was assassinated, leaving no legitimate heirs. The 17-year-old Cosimo was chosen to succeed him.
He proved a formidable ruler, and in 1569 he was granted the more prestigious title of Grand Duke of Tuscany. His wife was Eleonora of Toledo, born in 1522 in Salamanca, the daughter of a Spanish aristocrat who governed Naples. Their marriage in 1539, when Eleonora was 17, cemented an alliance between the Spanish and the Medici. The couple produced 11 children—seven boys and four girls—a number considered exceptionally successful for an early modern dynasty.
Two of the sons died in infancy, and two others, Giovanni and Garzia, died of malaria in 1562 within weeks of each other. The eldest, Francesco, succeeded his father in 1574, and Ferdinando succeeded him in turn. One son, Pietro, proved psychologically unstable and violent, a source of lasting embarrassment to the family. But it was the daughters whose fates would become the darkest chapter of the Medici story.
Even before his marriage, Cosimo had fathered a daughter. Bia de’ Medici was born around 1536, her mother’s identity kept secret. Despite her illegitimacy, Cosimo claimed her and brought her into the household. Eleonora, though only her stepmother, treated her with kindness.
Bia was raised at the family estate of Villa di Castello under the care of her grandmother, Maria Salviati, alongside another illegitimate Medici girl, Giulia. Cosimo adored Bia and made it clear she remained his favorite even after the birth of his legitimate children. But after returning home from a journey with her father, the six-year-old fell suddenly ill with a high fever, likely malaria, and died on March 1, 1542. Cosimo commissioned a posthumous portrait from the court painter Agnolo Bronzino, producing one of his most haunting works.
The next daughter to die was Anna, born March 19, 1553, the second youngest of the couple’s children. She died less than five months later, on August 6. Virtually nothing is known of her brief life or the circumstances of her death. Infant and child mortality were common in the 16th century, with as many as a third of children dying before their early teens.
Anna was one such victim. Maria de’ Medici, the eldest of Cosimo and Eleonora’s children, was born on April 3, 1540. She grew up in a warm family environment; Cosimo and Eleonora genuinely loved their children and took a close interest in their upbringing, unlike many royal parents of the era. But the children also served a political purpose.
In an Italy divided between Spanish and French influence, advantageous marriages were essential. When Maria was only five, her portrait was sent to her cousin Catherine de’ Medici in Paris, a sign that a prestigious French marriage was already being considered. In the end, a different alliance was arranged: Cosimo betrothed Maria to Alfonso d’Este, son of the Duke of Ferrara. Before the wedding could take place, however, Maria fell ill, likely with malaria, and died on November 19, 1557, at 17.
Scandalous whispers swept Florence, claiming Cosimo had stabbed her in a rage after discovering a secret love affair, but the story was almost certainly court gossip, given his known affection for his children. The marriage alliance with the Este family was not abandoned. Lucrezia de’ Medici, born February 14, 1545, was simply substituted for her dead sister. This was not even her first proposed match: at age seven, plans had been made for her to marry the nephew of Pope Julius III, a plan that collapsed with the Pope’s death in 1555.
In July 1558, at just 13, Lucrezia married the 24-year-old Alfonso d’Este. After the ceremony, Alfonso returned to his father’s court, leaving his young bride behind in Florence. He then departed for France to help negotiate the Treaty of Cateau-Cambrésis, which finally ended decades of war between France and Spain. Lucrezia remained in limbo, married in name but effectively abandoned.
When the Duke of Ferrara died in October 1559 and Alfonso ascended as Duke Alfonso II, Lucrezia was finally summoned. She arrived in Ferrara as the new duchess at just 14. Bronzino later painted her, capturing her unnaturally pale complexion—a fashionable ideal, yet perhaps also a hint of fragile health. By 1561 she was plagued by recurring fevers, confined to her rooms.
Cosimo sent his own physicians, but nothing slowed her decline. Whispers of poison circulated, but modern historians dismiss the tales; the evidence points to pulmonary tuberculosis. On April 21, 1561, at 16, Lucrezia died in Ferrara. Only Isabella remained.
Born August 31, 1542, she had been married at 11 to Paolo Giordano Orsini, a member of one of Rome’s oldest aristocratic families, who claimed descent from Julius Caesar. The marriage was arranged in 1553, yet another politically advantageous match. Duke Cosimo, wary of his son-in-law’s spendthrift ways, kept Isabella in Florence with a large dowry until he saw proof that Paolo would not squander the money. She eventually left for Rome, where she suffered a series of miscarriages before finally giving birth to two healthy children: a daughter, Francesca, in 1571, and a son, Virginia, the following year.
By then, Cosimo had endured heartbreaking losses, including the death of his wife Eleonora in 1562, who died of malaria at 40 alongside two of their sons. Cosimo himself died in April 1574, succeeded by Francesco. The new Grand Duke gave tacit support to a brutal series of reprisals against perceived infidelities among Medici women. Isabella had been carrying on a 12-year affair with Paolo’s cousin, Troilo Orsini, begun in 1564 after she lost a child during pregnancy.
The affair had become too public to be tolerated. On July 16, 1576, Paolo strangled Isabella at the hunting lodge. Her brother Francesco supported the act. Six days earlier, Pietro had strangled his own wife, the young ward Eleonora di Toledo, with a dog leash.
Cosimo’s only surviving legitimate daughter was murdered by her husband with her own brother’s approval, in revenge for having embarrassed the family through adultery. A striking reminder of how brutal life could be for aristocratic women in early modern Europe, the fates of the Medici girls demonstrate how daughters of a ruling dynasty were treated first as political pawns to secure alliances and then, when they became inconvenient, violently discarded. Of all of Cosimo’s daughters, only one lived past 40: Virginia, born in 1568 to Cosimo’s mistress Camilla Martelli. She married the Duke of Modena in 1586 and bore ten children, but later showed signs of severe mental illness, with her confessor claiming she was possessed by demons.
She died in 1615 at 46. The rest of the Medici girls met earlier ends—by illness, by murder, or, in one case, in infancy—leaving behind only portraits that still hint at the tragedy that cut their lives short.