The New Adventures Of Old Christine actress took the conservative radio talkshow host to task during the White House Correspondents' Association Dinner on Saturday night, TV Guide reports.
The comedienne touched on Limbaugh’s much-publicised dependency upon prescription drugs, while she also equated him to Osama Bin Laden.
Sykes further admonished the DJ for his views on the current US administration.
She said: "Rush Limbaugh said he hopes this administration fails. So you're saying, 'I hope America fails.' You're like, 'I don't care about people losing their homes, their jobs, our soldiers in Iraq.' He just wants the country to fail. To me, that's treason."
Joy Behar, a fellow comic and co-host on The View, said that comedians who perform at this event often find themselves in trouble and defended Sykes.
Behar added: "People are going after her because she went over the line with Rush Limbaugh - erm, hello? Rush Limbaugh goes over the line on a regular basis."