As Argentina's all-time appearance holder and record scorer, Messi remains the first name on the teamsheet and barring any unforeseen fitness issues, he will feature in his 35th Copa America match at the Mercedes-Benz Stadium.
Meanwhile, the 2022 World Cup Golden Glove winner Emiliano Martinez will be entrusted with being entrusted with guarding the net, and the Aston Villa goalkeeper is expected to be shielded by the central defensive pairing of Cristian Romero and Nicolas Otamendi.
Atletico Madrid's Nahuel Molina is poised to operate on the right side of the back four, while Marcos Acuna may get the nod over Nicolas Tagliafico at left-back.
Rodrigo De Paul is a certain starter in midfield, but there is some doubt as to which two players will join him in the engine room.
Alexis Mac Allister and Leandro Paredes are seemingly the favourites to join De Paul, although they are facing competition from Chelsea's Enzo Fernandez, who has returned to fitness following groin surgery.
Messi could be joined in attack by Fiorentina's Nicolas Gonzalez, who has started six of Argentina's seven qualifiers for the 2026 World Cup.
Lautaro Martinez finished the 2023-24 campaign as Serie A top scorer and netted two goals in the recent 4-1 win over Guatemala, but the Inter Milan forward is still expected to miss out on a starting berth.
Julian Alvarez is poised to start over Martinez after enjoying a successful season with Manchester City, scoring 19 goals and providing 13 assists in 54 competitive matches.
Argentina possible starting lineup: Martinez; Molina, Romero, Otamendi, Acuna; Mac Allister, Paredes, De Paul; Messi, Gonzalez, Alvarez