Updated at 6:02 p.m. ET
Citing his ailing health, Sen. Thad Cochran, R-Miss., announced he will resign on April 1, setting up a special election this November.
"I regret my health has become an ongoing challenge," Cochran said in a statement Monday. "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, 80, chairs the Appropriations Committee and has been absent from the Senate for long stretches over the past year, and his resignation does not come as a surprise. However, it does mean that both of Mississippi's Senate seats will be on the ballot come November.
According to state law, the remainder of Cochran's term, which expires in 2020, will be filled by a nonpartisan special election in conjunction with the regularly scheduled general election. If no candidate, regardless of party, gets 50 percent, it will go to a December runoff. In the meantime, Republican Gov. Phil Bryant will appoint an interim senator.
The state's other senator, Republican Roger Wicker, is also up for re-election this year. He drew a primary challenge last week from state Sen. Chris McDaniel, who previously challenged Cochran in a particularly nasty fight in 2014. McDaniel actually topped Cochran in the first primary election, but failed to get a majority. In the runoff, with the help of crossover Democratic and African-American voters, Cochran prevailed.
In a statement later Monday, McDaniel left open the possibly of switching from challenging Wicker to the now-open seat, saying that he would "continue to monitor developments regarding his replacement and the Special Election that will follow."
"While it is certain that Mississippi will have two U.S. Senate races this year, I am currently focused on my campaign against Roger Wicker, but all options remain on the table as we determine the best way to ensure that Mississippi elects conservatives to the United States Senate," McDaniel said.
Cochran was first elected to the Senate in 1978 — the first Republican elected statewide then in over 100 years — and had previously served three terms in the House. He leaves as the 10th-longest-serving U.S. senator ever.
"It has been a great honor to serve the people of Mississippi and our country. I've done my best to make decisions in the best interests of our nation, and my beloved state," Cochran said in announcing his decision to step aside. "My top concern has always been my constituents in Mississippi. My hope is by making this announcement now, a smooth transition can be ensured so their voice will continue to be heard in Washington, D.C. My efforts, and those of my staff, to assist them will continue and transfer to my successor."
The Jackson Clarion-Ledger noted that Cochran was a well-liked member of the Senate, dubbed "Gentleman Thad" by his fellow legislators, and that he was known for his "quiet stately demeanor" and often played "piano to relax in his office." Time magazine once called him "The Quiet Persuader" for his ability to work across the aisle.
His perch atop the powerful Appropriations Committee — which he held during the mid-2000s before regaining it again when Republicans took back the Senate in 2014 — also allowed him to direct projects and money back home to Mississippi, including agricultural aid, funding for universities and federal contracts. That "bringing home the bacon," however, drew the ire of fiscal conservatives and was the reason that many of them supported McDaniel in his 2014 primary challenge.
But that same influence also proved critical after Hurricane Katrina in 2005, allowing him to steer billions of dollars to the state. "The federal relief he helped secure is credited with preventing financial and social ruin in Mississippi and Louisiana after the hurricane's destruction," the Clarion-Ledger wrote.
Former Gov. Haley Barbour wrote in his book America's Greatest Storm that the way Cochran was able to build bipartisan consensus to deliver aid to the devastated states along the Gulf of Mexico helped save Mississippi.
"On the Senate side, Thad Cochran was in charge, and few if any senators were of a mind to question what he wanted to do for the states hit by Katrina," Barbour wrote. "[Cochran] is a quiet, polite gentleman, but he is tough as nails."
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