The Argentine, who won the Champions League and two of his La Liga titles with Neymar alongside him at Barcelona, said he had spoken to the Brazilian about rumours linking him with a return to Spain.
"It would be terrible, because of all that Ney means to Barcelona," Messi told Argentina's TyC Sports. "If he ends up at Real Madrid it would be a major blow to us. And on a footballing level Madrid would be much stronger than they already are."
When asked if he had told the Brazilian not even to think about going to Madrid, a smiling Messi said: "He knows what I think, I’ve already told him!"
Neymar left Barcelona last August, becoming the world's most expensive football player in a transfer that upset many Barcelona fans.
Yet media reports that he might leave the French capital and move to Madrid have been circulating for months, prompting the PSG chairman to declare earlier this week that Neymar will "2000 percent" be in Paris next season.
The Brazilian has refused to talk about the speculation and said he is concentrating on recovering from a foot injury in time for next month's World Cup.
Messi, the five-times World Player of the Year, said he was looking forward to the tournament in Russia and was targeting at least a semi-final place with Argentina.
Beaten finalists four years ago in Brazil, Argentina have not won a major international title since 1993 when they lifted the Copa America.
They reached the final of the same tournament in 2015 and 2016 but lost both times and Messi said the successive failures weighed heavily.
"It's a weight that we carry and we want to overcome it," he said.
Argentina kick off their World Cup campaign against Iceland on June 16 and then face Nigeria and Croatia.
They have struggled under coach Jorge Sampaoli, who took over last year and has won just five of his 10 games in charge.
Argentina beat Italy 2-0 in a March friendly but that victory was sandwiched by a 4-2 loss to Nigeria and a 6-1 hammering by Spain.
Spain are one of the favourites for the tournament, Messi said, along with Brazil, Germany and France.
(Reporting by Ramiro Scandolo, Writing by Andrew Downie; Editing by Toby Davis)
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