The USCPA is concerned for the welfare of the mother of the puppies dumped close to Ballyconnell.
On Monday, three Labrador-cross pups were found on the Gortaree Road in Fermanagh, between Derrylin and the border.
They were "cold to the touch" and still had their umbilical cords attached when they were taken into the care of the charity.
One of the pups has since died, but the other two are said to be recovering well.
An appeal is being made for information as to how they ended up in a ditch.
Development Manager with USPCA, Colleen Tinnelly says the mother of the dogs has yet to be located.