Italy beat Namibia 52-8 in their Pool A opener in a scoreline that flattered the Azzurri. Uruguay impressed in a 27-12 defeat to France, going toe-to-toe at times with their far more illustrious host.
With New Zealand also in their group, the best Italy and Uruguay are likely to achieve is third place and a direct spot at the next World Cup.
Kieran Crowley has brought in Marco Riccioni, Niccolo Cannone, Alessandro Garbisi and Lorenzo Pani for the match in Nice on Wednesday.
But perhaps the biggest surprise is moving Paolo Garbisi — Alessandro's older brother — from five-eighth to centre. It will be Garbisi's first test as No. 12.
That allows Ange Capuozzo to play in his best position as fullback, while Tommaso Allan returns to five-eighth.
The Azzurri start with two sets of brothers in a World Cup game for the first time as Lorenzo Cannone — Niccolo's younger sibling — has again been selected at No. 8.
Uruguay coach Esteban Meneses has brought in hooker German Kessler to replace Guillermo Pujadas, who drops to the bench, and wing Gaston Mieres comes into the starting XV for Bautista Basso, also now among the replacements.
ITALY
Italy: Ange Capuozzo, Lorenzo Pani, Juan Ignacio Brex, Paolo Garbisi, Montanna Ioane, Tommaso Allan, Alessandro Garbisi, Lorenzo Cannone, Michele Lamaro (capt), Sebastian Negri, Federico Ruzza, Niccolò Cannone, Marco Riccioni, Giacomo Nicotera, Danilo Fisichetti.
URUGUAY
Mateo Sanguinetti, German Kessler, Ignacio Peculo, Felipe Aliaga, Manuel Leindekar, Manuel Ardao, Santiago Civetta, Manuel Diana, Santiago Arata, Felipe Etcheverry, Nicolas Freitas, Andres Vilaseca (capt), Tomas Inciarte, Gaston Mieres, Baltazar Amaya
17°C