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"We respect the choice the people of the United Kingdom have made," the presumptive Democratic presidential nominee said.
Clinton continued: "Our first task has to be to make sure that the economic uncertainty created by these events does not hurt working families here in America."
The UK shocked the world on Thursday when it voted to bolt the EU. Markets plunged into chaos and British Prime Minister David Cameron announced he would resign his post later this year.
Clinton said it was important the US "make clear America's steadfast commitment to the special relationship with Britain and the transatlantic alliance with Europe."
She also took a swipe at her Republican opponent, Donald Trump.
"This time of uncertainty only underscores the need for calm, steady, experienced leadership in the White House to protect Americans' pocketbooks and livelihoods, to support our friends and allies, to stand up to our adversaries, and to defend our interests," Clinton said. "It also underscores the need for us to pull together to solve our challenges as a country, not tear each other down."
President Barack Obama shared a similar sentiment with Clinton, saying Friday that "the people of the United Kingdom have spoken" and "we respect their decision."
Trump, however, took a starkly different position. The New York businessman cheered the UK's decision and drew parallels between the so-called Brexit vote and US general election.
"They took their country back, just like we will take America back," he said.