At the age of 20, Louise was described as a beautiful and delicate tall, blonde girl with a white complexion, light brown eyes (veiled by a slight myopia), with a slender and refined silhouette.

Described as a "sweet and virtuous" young woman, Louise reportedly immediately and deeply fell in love with her husband, a feeling that never changed, despite the difficulties, tragedies, his infidelities and finally death.

Being a pious and very simple person, she is said to have suffered terribly because of the conflicts between her family (the Houses of Guise and Lorraine and in particular between her brother Philippe Emmanuel, Duke of Mercœur) and her husband during the Wars of Religion.

As a result, the heir presumptive was (after the death of the King's brother Francis, Duke of Anjou in 1584) the controversial Henry III of Navarre, a fact which placed additional pressure upon both Louise and her husband.

According to Brantôme, Louise was at one point advised by a lady-in-waiting, that because her marriage would not result in children, it would be wise to use a different method to accomplish this (referring to another biological father), but the Queen took deep offense at this advice and refused to listen.

Due to this popularity, in 1588 she proved a moral symbolic support for the royal cause when she remained in Paris with her mother-in-law after the King had fled from the capital during his conflict with the Duke of Guise.

Following her husband's death and for the next 11 years, Louise lived at the Château de Chenonceau, which she received as inheritance from her mother-in-law; she installed her room on the second floor, and she covered the walls with black.

But the castle being mired in debts and having not itself a huge pension, she bequeathed it to her niece Françoise of Lorraine, the only surviving child and heiress of her brother, who later married César de Bourbon, Duke of Vendôme (illegitimate son of King Henri IV and Gabrielle d'Estrées).