The 34-year-old has only just recovered from a bout of coronavirus and the Argentine FA have come to an agreement with Paris Saint-Germain for him to remain in France.
The absence of Messi and Joaquin Correa – who is ruled out with a hamstring injury – could provide an opportunity for Manchester City transfer target Julian Alvarez to be handed his first start for the national team, joining Lautaro Martinez and Angel Di Maria in attack.
Cristian Romero is continuing his recovery from a hamstring injury, so Nicolas Otamendi is set to be joined at centre-back by either German Pezzella or Lucas Martinez Quarta, shielding goalkeeper Emiliano Martinez.
Left-back Nicolas Tagliafico – who has been linked with a move to Barcelona this month – will be competing with Marcos Acuna for a place in the first XI, with either Gonzalo Montiel or Nahuel Molina, who have 13 international caps apiece, likely to operate at right-back.
Leandro Paredes, Rodrigo De Paul and Giovani Lo Celso all started in the goalless draw against Brazil last time out and the midfield trio could retain their places, though Guido Rodriguez and Alexis Mac Allister will be pushing for a starting role in Calama.
Emiliano Buendia, who is the only uncapped player in the Argentina squad, will also be hoping to force his way into the starting lineup, but a place on the substitutes' bench to begin with is more likely, along with the likes of Maximiliano Meza, Nicolas Gonzalez and Lucas Ocampos.
Argentina possible starting lineup: E. Martinez; Molina, Pezzella, Otamendi, Acuna; Lo Celso, Parades, De Paul; Alvarez, L. Martinez, Di Maria