Representatives Mike McIntyre (D-N.C.) and Carolyn McCarthy (D-N.Y.) are retiring, according to Democratic party sources.
McIntyre would have been a top target of Republicans in 2014, despite his opposition to the Affordable Care Act and more conservative voting record. He was considered to be one of the last "Blue Dog" Democrats in Congress.
Republican presidential candidate Mitt Romney won McIntyre's district by a 19-point margin in 2012. McIntyre beat his Republican challenger David Rouzer by only 654 votes, the closest margin of any House race in the nation.
McCarthy, who announced in June that she was undergoing treatment for lung cancer, was nationally-recognized as an advocate for gun control in Congress. She told Newsday that she decided, after struggling with health issues, that it was time to let someone new represent her district.
President Barack Obama carried McCarthy's seat by 12 points in 2012.
Sam Stein contributed to this report.