"While suffering from a stomach virus, Secretary Clinton became dehydrated and fainted, sustaining a concussion," Clinton's top aide Philippe Reines said in a statement.
The news came just as Clinton, 65, had been expected to testify on Thursday to US lawmakers about the findings of a highly-anticipated investigation into September's militant attack on the US consulate in Benghazi, Libya.
The normally indefatigable Clinton, who in her four years as the top US diplomat has travelled almost a million miles visiting 112 countries, was "recovering" but plans to stay away from the office next week.
"She has been recovering at home and will continue to be monitored regularly by her doctors," Reines added.
At their recommendation, Clinton "will continue to work from home next week, staying in regular contact with Department and other officials."
There are also a slew of Christmas festivities planned at the State Department next week that Clinton had planned to host.
Clinton has already been out of the public eye for the past week, after she had to cancel a trip to North Africa when she contracted the stomach virus on her return from a five-day visit to Europe.
"The secretary's been really very ill. I mean, very. This stomach virus is a pretty vicious one," State Department spokeswoman Victoria Nuland said Wednesday, adding the condition was not life-threatening.
The former first lady and wife of ex-president Bill Clinton is the most popular member of President Barack Obama's cabinet, with approval ratings of over 60 percent.
Even though she aims to step down as secretary of state early next year, Obama has not yet revealed his pick to replace her. Many believe that she will also take a second shot at being elected America's first woman president in the 2016 White House race.
This week she denied again she was planning to run in 2016, but said that although she is looking forward to a rest as she is exhausted after spending two decades in the public eye, her age would not play a factor in any decision.
"I am, thankfully, knock on wood, not only healthy, but have incredible stamina and energy," she told ABC.
She had been due to publicly testify on Thursday at open hearings in both the House and Senate on the outcome of the State Department investigation into the Benghazi assault in which the ambassador and three other Americans died.
State Department acting deputy spokesman Patrick Ventrell confirmed Friday the report should be completed by early next week. Its findings are not binding, but "it's a chance for the department as a whole to look at our operations and look at what needs to be done to improve security," he said.
Clinton has said she takes full responsibility, repeatedly stressing that no one wants to find out what happened in Benghazi more than she does.
The September 11 attack became a political punch bag in the final, furious weeks of the 2012 presidential elections, and has already complicated Obama's calculations for his second term cabinet.
The report's findings are also likely to ignite another storm of protest, with Republicans already scenting blood.
Republicans have castigated the administration for failing to provide proper security, and for employing local Libyan security staff.
Republicans also allege the administration sought to cover up the links to Al Qaeda by initially insisting the attack was sparked by a protest over an anti-Islam video, which had earlier triggered fury in Cairo.
The Republican onslaught cost US envoy to the United Nations, Susan Rice, her hopes of succeeding Clinton. Rice appeared on the Sunday talk shows just days after the assault to say that, according to the intelligence available, it arose from a "spontaneous" demonstration.
On Thursday, Rice asked Obama to withdraw her name from consideration to be the next top US diplomat, saying it would only lead to a protracted fight after several Republicans threatened to block her nomination.
Veteran Senator John Kerry, the chairman of the Senate Foreign Relations Committee, is now the odds-on favourite to replace Clinton at the helm of the State Department - an ambition he has long cherished.