"He's not going to be mayor of New York. He should go away," Axelrod, a former senior adviser to President Barack Obama, said on NBC's "Meet the Press."
Weiner resigned from Congress in 2011 after admitting to sending sexual photographs and messages to women over the Internet. He previously claimed to have been rehabilitated from such behavior through therapy since giving up his House seat, but admitted last week he continued to engage in the practice through most of last year.
"I would say the issue here isn't about his relationship with his wife, the issue is about his relationship with the voters," Axelrod said. "He's twice deceived them, lied about his activity, and why would you trust in someone who did that?"
"But I think that he is delusional at this point and doesn't understand the situation."