Longtime Republican U.S. Senator Thad Cochran says he will resign April 1 because of health reasons.
Cochran, who is 80 years old and has represented Mississippi in the Senate since 1978, has been ill in recent months, missing several weeks of voting late last year.
"I regret my health has become an ongoing challenge,'' Cochran said in a statement. "I intend to fulfill my responsibilities and commitments to the people of Mississippi and the Senate, through the completion of the 2018 appropriations cycle, after which I will formally retire from the U.S. Senate.''
Cochran is chairman of the powerful Senate Appropriations Committee, and his departure means Mississippi will have two Senate elections on the ballot this November.
His exit will affect the battle for the Senate majority, forcing Republicans to defend another seat during this year's midterm elections.
Republicans currently hold a 51-49 advantage over Democrats in the Senate. Midterm elections are historically difficult for the president's party to retain seats, and Republicans have little room to lose in the effort to remain in control of the chamber.
The other Mississippi Senate seat is held by Republican Roger Wicker, who is up for re-election this year.
Cochran's temporary replacement will be chosen by Mississippi's governor. A special election will be held in November to fill the rest of Cochran's term, which runs through January 2021.
When Cochran was first elected to the Senate in 1978, he became the first Republican in more than 100 years to win a statewide election in Mississippi. Now the state, along with many others in the south, regularly sends Republicans to Washington.
Cochran served six years in the House of Representatives before joining the Senate, putting his time in Congress at over 40 years.