The Fenerbahce central defender who faced Messi twice during the South American qualifiers told Reuters in an interview that Messi would only stand out at the South Africa finals if Argentina do well.
"For Messi at the World Cup it can get a bit more difficult because the matches will be tighter," Lugano said, speaking from Turkey.
"Opponents are going to mark him very hard and although he will make a difference because he is out of this world, it will be tougher (for him than in other tournaments).
"It's also going to depend a lot on how things go for his national team for him to stand out but there's no doubt we're talking about one of the most spectacular players of all time."
Messi soared to new heights with four goals when Barcelona beat Arsenal 4-1 at home in the second leg of their Champions League quarter-final on Tuesday.
However, FIFA's World Player of the Year has struggled to translate his Barcelona form to Argentina and was criticised at home for a perceived lack of commitment.
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Diego Maradona's Argentina will be looking to end a 24-year wait for the country's third title at the finals starting on June 11. They face Nigeria, South Korea and Greece in Group B.
Uruguay, who also have two titles dating back to the first half of the last century, are in a tough Group A with the host nation, France and Mexico.
Lugano, 29 and yet to win his first cap when Uruguay last played at the finals in Asia in 2002, named Brazil midfielder Kaka and Messi's Barcelona team mate Xavi of European champions Spain as players who could also shine in South Africa.
"Spain are playing a game that is superior to all others, without doubt they will arrive at the World cup as big favourites, then at the World cup anything can happen, but there is proof they are the national team in the best shape," he said.
He said record five-times champions Brazil and Argentina, despite their qualification troubles, were also favourites with their background and world class players.
Germany and title holders Italy could also be expected to do well when it mattered.
"The historic teams will also be making their mark on the championship and I hope Uruguay can get in among them."
