suffering a concussion, but her office had insisted that she was recovering and the top US diplomat was expected back at her desk on Monday.
"In the course of a follow-up exam today, Secretary Clinton's doctors discovered a blood clot had formed, stemming from the concussion she sustained several weeks ago," Reines said in a statement.
"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 added, referring to a major hospital in Clinton's home state.
"Her doctors will continue to assess her condition, including other issues associated with her concussion. They will determine if any further action is required."
Reines did not elaborate further on her condition.
Clinton, 65, has been off work since her return from her last foreign trip on December 7, although her staff has said she has been working from home.
Her lengthy absence from public life had sparked claims from some of her fiercer critics that she is trying to avoid testifying in a congressional investigation into a deadly attack on a US mission in Libya.
Earlier this month, the State Department said Clinton had contracted a bad stomach virus during her five-day stay in Europe. She had to cancel a planned trip to North Africa and Abu Dhabi due to the illness.
A week later, Clinton's doctors said she had become severely dehydrated due to the effects of the stomach bug and had fainted, suffering a concussion.
They recommended she rest at home and avoid, through mid-January, the high-intensity travel she had been accustomed to taking as secretary of state.
Clinton has flown almost a million miles since taking office four years ago, visited 112 countries and spent some 400 days in a plane.
Her health kept her from testifying on December 20 to US lawmakers about the attack on the US diplomatic post in the eastern Libyan city of Benghazi on September 11.
The assault, in which the US ambassador and three other American officials were killed, sparked a political firestorm in the United States, and Republicans criticized Clinton's absence from the hearings, calling on her to testify in January.
Clinton, who is due to step down from her post in early 2013, also stayed away from the White House last week when President Barack Obama nominated her replacement, veteran Senator John Kerry.
She issued a statement paying tribute to her successor.