The 'Candy Shop' rapper – whose real name is Curtis Jackson – believe the mental illness is a condition many people "can't afford" to take steps to deal with because their "responsibilities" give them no choice but to carry on as normal.
Speaking on the 'Big Boy's Neighborhood' radio show, he said: "Certain things I don’t believe in, based on … I think the things you go through make you who you are. And in my journey, there’s certain things that I don’t even let into my system like that.
“I think depression is a luxury. Where I’m from, you can’t afford to be depressed."
The 47-year-old star insisted mental health crises shouldn't get in the way of everyday obligations.
He added: “You gotta pay the bills, right? So you gotta go to work.
“You gotta get up, gotta go do what you gotta do. You got people right now that’s at work that don’t feel like being there. But they got responsibilities so they feel uncomfortable while they’re working, while they’re doing what they gotta do.
“When these guys get in a slump and they just decide they’re not gonna do anything – I’m like, where they do that at?”
Elsewhere in the interview, 50 Cent admitted he wishes his friend and “G-Unit” collaborator Tony Yayo had enjoyed more mainstream success instead of himself so he could have focused on their business deals.
He said: “My solo album took off so big that I just brought them with me.
“So it was clear that it was me creating opportunity for everybody else in the crew, but we was all together. I wish it would have been Yayo, because then I coulda did all of the business.
“If he woulda did what 50 Cent did, then I would have been running the whole thing.
“It would still be two of us. He’d still be 50 Cent as the artist and I’d be the largest asset to us,” he said.