Graham, a prominent Republican voice on foreign policy, had recently returned from Ukraine, where he met with Ukrainian President Volodymyr Zelenskyy in Kyiv.
US Republican Senator Lindsey Graham has died following a "brief and sudden illness," his office has announced.
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In a statement, it said Graham, 71, had died on Saturday evening.
"Senator Graham's family appreciates prayers at this time and asks for privacy during this incredibly difficult period," the statement added.
The Senator, who represented the state of South Carolina, was elected to the United States Senate in 2002 after starting his career as a lawyer in the US Air Force. He had been serving as the chairman of the Senate Budget Committee up until his death.
A prominent Republican voice on foreign policy, Graham had recently returned from Ukraine, where he met with Ukrainian President Volodymyr Zelenskyy to discuss support for Kyiv and sanctions on Russia.
Graham was also a close ally of US President Donald Trump.
Responding to news of his death on Sunday, Trump called Graham "one of the greatest people and Senators I have ever known."
"He was always working, and was a true American Patriot. Lindsey will be greatly missed," he added.
In June, Trump described Graham as a "wonderful friend" and someone who had "always been there when I needed him" as he endorsed him for re-election to the Senate.
It came after Graham had expressed skepticism over Washington's "memorandum of understanding" with Tehran, saying he was "concerned that Iran’s view of the agreement seems different than what the American negotiating team is claiming."
Graham later praised the deal after holding a "very lengthy and productive discussion" on the matter with US special envoy Steve Witkoff.
"After this discussion, it is my opinion that signing the MOU will be beneficial to the United States, in as much as the Strait of Hormuz will begin to open, and the hostilities with Iran will stop," he wrote in a post on social media.