Hillary Clinton suffered a concussion earlier this month after fainting and falling down.
At the time, she was reported to have had a stomach virus and to have passed out after becoming dehydrated.
Hillary Clinton is due to stand down as secretary of state before US President Barack Obama officially begins his second term in January.
Doctors discovered the clot during a follow-up examination on Sunday, her spokesman Philippe Reines said.
“She is being treated with anti-coagulants and is at New York-Presbyterian Hospital so that they can monitor the medication over the next 48 hours,” he said.
“They will determine if any further action is required.”
Hillary Clinton is due to give evidence before a Congressional committee in January in connection with the attack in September on the US consulate in the Libyan city of Benghazi.
The US ambassador to Libya and three American officials were killed in the incident.
Hillary Clinton was appointed secretary of state at the start of Barack Obama’s first term, in January 2009.
Her most recent foreign trip was to Dublin earlier this month.
Hillary Clinton, 65, is known for her gruelling travel schedule.
She is the most travelled secretary of state in history, having visited 112 countries while in the job, the Associated Press says.
Earlier this month, President barack Obama nominated Senator John Kerry – the Massachusetts Democrat who heads the Senate Foreign Relations Committee – to replace Hillary Clinton as secretary of state.
Hillary Clinton has repeatedly said that she only intended to serve one term in the post.
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