While Real Madrid's Ronaldo will also be bitterly disappointed to be heading home earlier than planned from Russian Federation, he at least has the consolation of having won his country's first ever European Championship, two years ago in France.
The teams will face off at 2 p.m. ET on Saturday in Sochi, Russia, in the 2018 World Cup Round of 16.
But just hours after Messi and Argentina had lost 4-3 to France, Cristiano was also on his way to the airport after his Portugal side lost 2-1 to Uruguay.
Cristiano Ronaldo insists now is "not the right time" to talk about his global future in the wake of Portugal's 2-1 loss to Uruguay in the World Cup round of 16.
Uruguay had not conceded a goal at this World Cup before Pepe rose unmarked to nod in an equaliser from close range, prompting a brief spell of dominance for Portugal.
Remarkably, neither Ronaldo nor Messi have managed to score a single goal in a knockout tie in four World Cups going back to 2006. Record-breaking captain Cristiano Ronaldo starred with four goals including a hat-trick against Spain and the victor against Morocco.
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Uruguay played a flawless group stage against relatively weak opponents to make it to the Round of 16, but the South American side proved it has what it takes to make a deep run at the World Cup by sending the reigning European champions home on Saturday.
"We have a team with many young players and of course we all want him there with us".
"The future? It's not the time to talk about the future in terms of players, coach".
It is an accusation often levelled at Portugal that they are a toothless team if Cristiano Ronaldo has an off day, but their victory in the Euro 2016 final with their talisman missing most of the game through injury is used as the ideal riposte to that suggestion.
"I believe that Ronaldo is one of the best strikers in the world", Tabarez said.
Santos had said: "Cristiano still has a lot to give to football".
Cavani applied a fine finish to Rodrigo Bentancur's pass in the second half to seal the win.