Barca and Real Madrid have a fierce Clasico rivalry and they're competing for the league and the Champions League this season.
Pique, 30, asked why the likes of Cristiano Ronaldo escape any accusations from the press and in courts in Spain.
"The thing I don't like about Madrid is its directors' boxes, the things that happen there: accusations for Messi, Neymar and nothing for Ronaldo," he told reporters after featuring in Spain's 2-0 victory over France on Tuesday in a friendy notable for being decided by video technology.
"We all know what goes on in the Madrid box, it's always been like that. I consider all of Madrid's players friends, but as a club, what do you want me to say?
"Is it the judge who accuses, not Madrid? Well, we know who it is, and how it all works. That's how I feel. I'm not going to argue about this."
"When did the referees favoured us? In the Champions League? Ah, I thought the question was about the league. In the league it has been a while.
"We are discussing an historic comeback of 6-1 and you focus on the referees. And when Real Madrid win a Champions League with an offside Sergio Ramos goal, nothing happens."
Pique added, knowing his quotes would be widely reported: "With this lovely mixed zone you're going to get the headline from me."
Neymar is currently facing charges of fraud over his transfer to Camp Nou in 2013, which was estimated to have cost Barca around €86 million.
Last year Ronaldo's agent released full details of his estimated £190m fortune in an effort to silence questions about his tax affairs.
Barca are currently trailing Real Madrid by two points with 10 games to play, having one less match in their favour.
They reached the Champions League quarter-finals - where they will play against Juventus - in memorably dramatic style by coming back from a 4-0 first leg defeat to eliminate PSG 6-5 on aggregate.