The United Kingdom's blockade of France, and the loss of several of his ships at sea, forced William Seton into bankruptcy.
From 1801 to 1803, the family lived in a house at 8 State Street, on the site of the present Church of Our Lady of the Most Holy Rosary.
In 1803, on the advice of doctors who thought a warmer climate might ease his condition, he set sail for Italy accompanied by Elizabeth and their eldest daughter Anna Maria.
This was not well-received by members of her social circle, and efforts to support her family by conducting a small school for young ladies were unsuccessful.
At the invitation of Sulpician Louis William Valentine Dubourg, in 1809, Elizabeth and her children moved to Emmitsburg, Maryland, where she opened Saint Joseph's Academy and Free School for girls.
Although Catherine spent most of her time in Emmitsburg, her mother sent her on occasional trips to Baltimore, Annapolis, and Philadelphia for her health and social enrichment.
In Baltimore, she made the acquaintance of Catherine Harper, daughter of Charles Carroll, one of the wealthiest men in America.
On her second trip, in company with Catherine Harper, she met Cornelia Connelly, who later founded the Society of the Holy Child Jesus.
Hughes had recently arranged for the Sisters of Mercy of Dublin to establish a presence in the diocese, and he suggested Catherine wait for their arrival.
She was affectionately called "the Angel of the Tombs" briefly during the Civil War while she acted as a far-stationed nurse for injured Union forces.