World Player of the Year Lionel Messi and Italian star Mario Balotelli have both been ruled out of the prestige friendly between Argentina and Italy on Wednesday after pulling out injured.
Messi's club Barcelona confirmed on Tuesday that the 25-year-old is suffering with a strain in his left leg while Balotelli's problem looks more serious after picking up a knee problem that could deprive him a place for AC Milan's crunch Champions League qualifier against PSV Eindhoven on August 20.
The former Manchester City striker was training with the Italian team during a visit from Pope Francis close to the Vatican when he broke down.
The 76-year-old pontiff who hails from Buenos Aires but is the son of Italian parents is scheduled to attend the match at the Olympic stadium in Rome.
"Leo Messi will not play the friendly in Rome this Wednesday between Argentina and Italy," read a Barcelona statement on the club's website.
"After undergoing a check-up with the Argentine medical staff it has been decided that the star will return to Barcelona to continue his recovery from a quadriceps strain in his left leg."
The 25-year-old missed the final match of Barca's Asian tour against Malaysia on Saturday with the injury.
However, the club are still hopeful that he will be fit to play on Sunday as the Catalans begin their La Liga title defence against Levante.