Sister Margaret Held and Sister Paula Merrill (pictured) were nurse practitioners and were found dead on Thursday morning when they did not report to work at a nearby clinic where they provided flu shots, insulin and other medical care for children and adults who could not afford it.
Sister Paula had worked in Mississippi for more than 30 years, according to the Sisters of Charity of Nazareth in Kentucky, originally from Massachusetts, she joined the order in 1979.
Sister Margaret was a member of the School Sisters of St Francis based in Milwaukee, she was a the order for almost 50 years.
Authorities have not yet said if they have a suspect for the attack in Durant.
A cause of death has not been released by police, however the Rev Greg Plata said police told him the nuns had been stabbed.
The bodies of the women, both 68, were taken to a state crime laboratory for post-mortem examinations.
Rev Greg Plata, who oversees the 35-member Catholic church where the sisters attended, said: "They were two of the sweetest, most gentle women you can imagine.
"Their vocation was helping the poor."
Spokesperson for the Catholic Diocese of Jackson, Maureen Smith, said there were signs of a break-in at the home and the nuns' vehicle was missing.
Authorities later said the car was discovered, abandoned on a secluded street barely a mile from the murder scene.
Authorities have not released a motive for the killings and it was not clear if the nuns' religious work had anything to do with the attack.
Durant assistant police chief James Lee, also a Catholic said: "I have an awful feeling in the pit of my stomach."
Officers are checking video from surveillance cameras in town.
A statement on the Sisters of Charity of Nazareth website asks people to "pray in gratitude for the precious lives of Sisters Paula and Margaret ... they served the poor so well. Because we are gospel women, please also pray for the perpetrators."
We pray in gratitude for the precious lives of Sisters Paula and Margaret ... they served the poor so well.— Susan Gatz (@susangatz) August 26, 2016
The Catholic community in Mississippi is relatively small, of almost three million people, the diocese says there are around 108,000 Catholics.
The two nuns provided almost all the care at the clinic and the investigation into their death is continuing.