Argentine media reported Messi suffered a sore left thigh on Sunday during Inter Miami's 2-1 victory over Atlanta United in Major League Soccer.
However, the Argentine Football Association did not disclose the reason for his absence.
Argentina, which leads South America, will visit second-placed Uruguay on Friday and host fifth-placed Brazil four days later at Monumental Stadium in Buenos Aires.
Messi was not the only absentee for th two matches that could seal Argentina's qualification. Also ruled out were Paulo Dybala, Gonzalo Montiel and Giovani Lo Celso.
Scaloni also dropped Alejandro Garnacho and Claudio Echeverri from the larger squad announced on March 2.
World Cup winner Messi has been sidelined several times by Inter Miami this season due to a risk of injury, Miami coach Javier Mascherano said.
This month, Messi missed three games but returned on Thursday for the second leg of the round-of-16 CONCACAF Champions Cup tie against Cavalier SC.
Mascherano said Messi was fit to start against Atlanta on Sunday. Messi scored in the 20th minute, just before he was reported to have been injured.
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