Agustin Creevy will replace number eight Agustin Guzman, who suffered a collar bone injury before Saturday's 60-13 victory against Chile.
The other change sees Horacio Agulla come in for Hernan Senillosa, who asked Loffreda to leave him out for personal reasons.
"I'm very happy to be included," said Agulla. "I wasn't expecting it because I thought that the same team who played Chile would face Uruguay.
"I watched the Chile game and I think Argentina played very well. Chile had a good defence, but Argentina knew how to break it."
If the Pumas win, as expected, they will be crowned South American champions and play in World Cup in Group D, alongside France, Ireland, the first team in the Africa group and a third-ranked European country.
Uruguay and Chile will clash for the last spot available for a South American country on July 22.
Mario Ledesma, Martin Scelzo (both ASM Montferrand), Miguel Avramovic (Alumni), Federico Todeschini (Beziers), Manuel Carizza (Biarritz), Pablo Gambarini (CASI), Marcos Ayerza (Newman), Pablo Bouza (Harlequins), Juan de la Cruz Fernandez Miranda, Horacio Agulla (both Hindu), Nicolas Vergallo (Jockey Club Rosario), Juan Manuel Leguizamon, Gonzalo Tiesi (both London Irish), Martin Durand (Montpellier), Rimas Alvarez (Perpignan), Martin Schusterman (Plymouth Albion), Gaston De Robertis (Regatas Bella Vista), Federico Serra Miras (SIC), Agustin Creevi (San Luis), Lucas Borges, Agustin Pichot (both Stade Francais), Rafael Carballo (Toulon).