Abedin's decision to separate comes in the immediate aftermath of the 'The New York Post' report that Weiner had sent explicit photos with his toddler son in the background to a woman.
"After long and painful consideration and work on my marriage, I have made the decision to separate from my husband," Abedin said in a statement.
Weiner, a seven-term democrat, had resigned in 2011 after it was disclosed he had been sending lewd messages to random women online.
According to the report, the woman, who spoke on condition of anonymity, the electronic chats between her and Weiner began in late January 2015 and continued through earlier this month.
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Asked for comment, Weiner said in the report that he and the woman "have been friends for some time."
Abedin, 40 and currently vice chairwoman of the Clinton Campaign, married Weiner in 2010. In December 2011, she gave birth to a boy Jordan Zain Weiner.
"Anthony and I remain devoted to doing what is best for our son, who is the light of our life. During this difficult time, I ask for respect for our privacy," Abedin said.
Considered as one of the closet personal aide to Clinton, Abedin has been in news of late in the aftermath of Clinton's email-scandal and release of emails of the former secretary of state.