She was the daughter of Simon Marie (1775–1855) an infantry captain in Napoleon's Grande Armée from a modest background, and Henriette Josephine de Ficquelmont (1780–1843), member of an old, but impoverished nobility of Lorraine.

In 1835 she had a marriage of convenience with an Amédée de Vaux, who helped her father at his office of tax collector in Méru, but her husband turned out to be nothing but a rogue.

Nonetheless she agreed to follow up with their correspondence and Comte's passionate love kept growing until Clotilde suddenly died of tuberculosis a year later.

Nonetheless, Clotilde's faith persuaded him to create a religion for positivist societies in order to fulfill the cohesive function once held by traditional worship.

Comte's secular religion is no vague effusion of humanistic piety, but a complete system of belief and ritual, with a calendar reform called the 'positivist calendar' (with Sainte Clotilde's day each April 6 and a Day of Holy Women), liturgy and sacraments, priesthood and pontiff, all organized around the public veneration of Humanity, the Nouveau Grand-Être Suprême (New Supreme Great Being) made after Clotilde de Vaux.