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Messi missed Inter's 4-1 win at the Houston Dynamo in Major League Soccer on March 2 and then the 2-0 midweek home win over Cavalier in the first leg of the last-16 tie against the Jamaicans.
The Argentine then sat unused on the bench for Sunday's 1-0 win over Charlotte in MLS, with Mascherano saying the caution over using the eight-time Ballon d'Or winner was based on managing his workload and not an injury.
Speaking to the media before the team flew out to the Caribbean island nation, Mascherano, a former team-mate of Messi's at Barcelona, said the forward would have been making the trip.
The game was expected to attract a sell-out crowd to the 35,000 capacity National Stadium in Kingston. While Messi has faced Jamaica's national team for Argentina, he has never played in the nation before.
