The 34-year-old snubbed a handshake from Mauricio Pochettino when he was hauled off in last weekend's win over Lyon, which was thought to have been a tactical change at the time.
However, it has since been revealed that Messi suffered a bone contusion on his left knee, and the six-time Ballon d'Or winner was forced to miss Wednesday's win over Metz.
The issue was not originally thought to be serious, but Spanish medical outlet Mejor con Salud suggests that Messi's knee injury could potentially keep him sidelined for the next few weeks.
The report adds that Messi may have sustained the original problem against Venezuela earlier this month and it has since flared up, which puts the attacker at risk of more serious injuries capable of ruling him out for months.
Messi is set for further tests on the issue this week but is already classed as a major doubt for next week's Champions League showdown with Manchester City at the Parc des Princes.
The former Barcelona man is yet to get going in Paris since his emotional exit from Camp Nou, registering no goals and no assists from his opening three games under Pochettino.