Paris Saint-Germain forward Ezequiel Lavezzi has been chosen as the man to replace Sergio Aguero in Argentina's attack, as the Albiceleste look to take first place in the Conmebol World Cup qualifiers with victory over Paraguay.
El Kun was already ruled out for Friday's match in the Estadio Mario Kempes after incurring a one-match suspension in the last qualifier against Ecuador, and was left in Buenos Aires to recover from injury after originally expecting to travel with the squad to Cordoba. Lavezzi will win his 19th international cap against Paraguay, while Rodrigo Brana also enters for the suspended Javier Mascherano.
Hugo Campagnaro is a further new face for the home side. Pablo Zabaleta was set to start on the right, but failed to prove his fitness in time and will be replaced by the Napoli defender and Cordoba native.
For Paraguay, there is a first competitive start for Cerro Porteno forward Jonny Fabbro. The 29-year-old, who was born in Buenos Aires but qualifies for Gerardo Pelusso's team through residency, partners Roque Santa Cruz up front.
Argentina (4-2-3-1): Romero; Campagnaro, Garay, Fernandez, Rojo; Gago, Brana; Di Maria, Messi, Lavezzi; Higuain.
Paraguay (4-4-2): Villar; Piris, Alcaraz, Da Silva, Ortiz; Ayala, Caceres, Riveros, Estigarribia; Fabbro, Santa Cruz.