The Inter Miami attacker picked up a "minor hamstring injury" in a CONCACAF Champions Cup clash with Nashville last week and will subsequently not be involved during the international break, joining Paulo Dybala and Exequiel Palacios (both thigh) on the sidelines.
Lisandro Martinez has earned a surprise call-up to the senior squad even though he has been sidelined since February 4 with a knee injury, but Manchester United have confirmed that the defender will not feature in either of Argentina's friendlies with El Salvador and Costa Rica this month and will instead "continue the final steps in his rehabilitation".
The absence of Martinez could see Nicolas Otamendi joined in central defence by Cristian Romero or German Pezzella, while Boca Juniors' Nicolas Valentini and Brighton & Hove Albion's Valentin Barco are two uncapped defenders seeking to make their debut.
Teenage Monza midfielder Valentin Carboni will also be looking to earn his first senior cap, although he faces stern competition from the likes of Enzo Fernandez, Alexis Mac Allister, Rodrigo De Paul and Guido Rodriguez for a start in Lionel Scaloni's side.
Alejandro Garnacho has impressed for Man United this season and the three-cap winger will be hoping to get some more international minutes under his belt in the absence of both Messi and Dybala, while Julian Alvarez, Lautaro Martinez and Angel Di Maria are among the other attackers at Scaloni's disposal.
Argentina possible starting lineup: E. Martinez; Molina, Romero, Otamendi, Tagliafico; Mac Allister, Fernandez, De Paul; Di Maria, L. Martinez, Garnacho