Uruguay don’t risk Luis Suarez against Costa Rica, so Diego Forlan starts with Edinson Cavani and Walter Gargano.
This Fortaleza match opens Group D and kicks off at 20.00 UK time (19.00 GMT), followed by Italy against England tonight.
Liverpool hitman Suarez has been in stunning form this season, but picked up a knee injury a month before the tournament.
Coach Oscar Washington Tabarez – who had a brief spell in charge of Milan – has preferred not to risk starting him in this game against Group minnows Costa Rica.
Instead, ex-Inter striker Forlan partners former Napoli hitman Cavani, while Juventus full-back Martin Caceres and Parma midfielder Walter Gargano also start.
Alvaro Pereira is still owned by Inter, but spent this season on loan in Brazil with Sao Paulo.
Costa Rica are seen by many as dark horses for Group D and could cause some upsets in this tournament.
Arsenal forward Joel Campbell is one to watch, although due to work permit issues he has been on loan at Olympiacos.
Bryan Ruiz can also provide danger for the Uruguayan defence, while Oscar Duarte is picked ahead of Johnny Acosta.
The history books do not look kindly on Costa Rica, who have only managed two draws from their total eight meetings with Uruguay.
Uruguay: Muslera; Pereira, Lugano, Godin, Caceres; Arevalo Rios, Gargano, Stuani, Rodriguez; Forlan, Cavani
Costa Rica: Navas; Gamboa, Umana, Gonzalez, Duarte, Diaz; Bolanos, Borges, Tejeda; Campbell, Ruiz