The squad will be boosted by the return of Manchester United striker Edinson Cavani, who recently served an international suspension.
Having netted 51 goals in 118 appearances for his nation, the 34-year-old should slot right back into the side to reform a potent front two alongside Luis Suarez.
Suarez will line up against his former Barcelona teammate Lionel Messi, having helped Atletico Madrid beat his old side to the La Liga title this season with 22 goals in the Spanish top flight.
In a clash with such a dangerous attacking side, Lucas Torreira should be deployed in midfield thanks to his impressive ability to win the ball back, as they will come up against a dynamic and quick midfield alongside a clinical front line.
He will shield the familiar centre-back pairing of Jose Gimenez and captain Diego Godin, with the pair having made a combined 203 international appearances and Godin holding the record for the most Uruguay caps with 143.
Experienced Fiorentina defender Martin Caceres will also play in the back four, having featured 104 times for his nation.
Uruguay possible starting lineup: Muslera; Gonzalez, Gimenez, Godin, Caceres; Torres, Valverde, Torreira, Rodriguez; Suarez, Cavani