The Argentine captain was forced off after an hour of the Copa America final against their upcoming opponents back in July, and has yet to make a full recovery, remaining with his club side Inter Miami for treatment.
Even without Messi, Argentina still turned on the style, beating Chile 3-0 last week, with Paulo Dybala being handed the legendary number 10 shirt, and scoring off the bench.
Dybala may have to watch on from the sidelines from the start again here though, with Julian Alvarez and Lautaro Martinez set to start in attack for Lionel Scaloni's side in Messi's absence.
Scaloni attempted a change in shape for the clash with Chile, starting in a 3-5-2 formation with Nicolas Gonzalez starting as a makeshift left wing-back, but shortly after the interval, Lisandro Martinez was moved out wide to left-back as they reverted to a four-at-the-back system.
That saw Giovani Lo Celso come on for Gonzalez, and Argentina looked more impressive following the switch, so Scaloni could opt to go with that from the outset here.
Elsewhere on the injury front, Bayer Leverkusen's Exequiel Palacios is currently out and has been joined on the sidelines by defensive duo Leonardo Balerdi and Nicolas Tagliafico.
Not getting regular minutes in Serie A for Fiorentina has seen Lucas Martinez Quarta lose his place in the squad for the time being, with Scaloni handing first call ups to a number of individuals this week.
Taty Castellanos has already made his debut as a late sub versus Chile, and Matias Soule, Giuliano Simeone, and Ezequiel Fernandez could follow suit here.
Soule has just made a big-money move to Roma over the summer and will have his eyes set on being the long-term replacement for Argentina icon Angel Di Maria, who announced his retirement from international football following the Copa America success.
Argentina possible starting lineup:
E Martinez; Molina, Otamendi, Romero, Li Martinez; De Paul, Mac Allister, En Fernandez, Lo Celso; Alvarez, La Martinez
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