The Daughters of Charity were especially unique in that they had been formally trained as nurses long before such programs were popular. By 1861, the Daughters had had over 30 years of nursing experience in both public and Catholic hospitals, as well as inner city missions. When the war broke out, 200 Daughters offered to nurse the wounded soldiers free of charge. The St. Francis deSales infirmary in Richmond, VA, accepted their offer and opened its doors to patients in July 1861. Several Daughters were also sent across town to St. Ann's Military Hospital, formerly an almshouse.

Conditions at St. Ann's were deplorable. There was little food for either patients or nurses. Chamber pots and bedpans were ordered to be dumped over the front porch. There were no clean hospital gowns or linens for the men, since the laundress had misunderstood directions and "watched" the dirty laundry, rather than "washing" it! Under the Daughters' supervision, the wards were transformed and the general sanitation improved greatly.

One particularly interesting incident occurred on June 26, 1863, when Union troops en route to Gettysburg made camp near the Daughters' headquarters in Emmitsburg. The Daughters had only a few loaves of bread to feed themselves and 80, 000 hungry soldiers. They resolved to cut the bread into small pieces and give it away to as many soldiers as they could, thus denying themselves. However, a miracle not unlike the Bibilical "loaves and fishes" incident occurred; somehow, just a few loaves of bread fed 80, 000 hungry men with enough left over for a substantial supper for the Daughters.

On July 6, 1863, three days after the great battle, Father Berlando took 12 Daughters and a wagonload of supplies to Gettysburg. En route, the wagon was fired upon by nervous Union troops, who mistook them for a wagonload of wounded Confederates. The little band arrived in town safely and set up headquarters in McCullough's Hotel. The Daughters were promptly put in charge of all volunteer nurses serving at the 113 hospitals in and around Gettysburg. The volunteer nurses often resented the Daughters' expertise; several tried to have the Daughters "fired" from their positions on the basis that the nuns were coercing men into deathbed conversions to Catholicism.

Often, the Daughters were the first to see the wounded men as they were brought in from the field hospitals. Many accounts of the battle's aftermath describe the heartrending scenes of the nuns dressing wounds, wiping bloody hands and faces, reciting the rosary over the wounded men, baptizing those who requested it. At the Pennsylvania College (now Gettysburg College) hospital, one Daughter went beyond the call of duty by acting as a referee. Two soldiers with minor wounds got into a fistfight; undaunted, the nun pushed herself in between the two men and pinned one man up against the wall, while holding back the other.
The Daughters also brought "goody baskets" to the men, containing jelly, medicinal whiskey, combs, handkerchiefs, and stationary to help the men feel more comfortable and at home in the hospitals. However, many of the nuns contracted lice during their visits to the hospitals and unwittingly took the lice home with them as unwanted "souvenirs" of the battle!