The Central Intelligence Agency lowered the flag to half-mast at its tightly guarded headquarters in the Washington suburb of Langley but did not release the casualties' names, who died cloaked in the same anonymity with which they lived.
"Your triumphs and even your names may be unknown to your fellow Americans, but your service is deeply appreciated," President Barack Obama wrote in a letter to CIA employees.
Obama said that since the September 11, 2001 attacks on the United States, "the CIA has been tested as never before."
"Because of your service, plots have been disrupted, American lives have been saved and our allies and partners have been more secure," Obama said.
He said stars would be added in their name to the 90 already on the Memorial Wall at CIA headquarters honoring spies who have fallen in the line of duty.
While more than 500 US and coalition forces have died in Afghanistan this year, Wednesday's suicide attack may show a new level of sophistication for the Taliban who infiltrated the very agency in charge of finding them.
The CIA said that a Taliban bomber managed to penetrate the defenses of a forward base in Khost, a pivotal province near the Pakistan border, detonating an explosives belt in a room described as a gym.
"This attack is something that will never be forgotten in Langley, Virginia," said Jack Rice, a former CIA officer in Afghanistan and talk-show host.
"The impact can be huge, not just in terms of the capabilities of these particular people, but in the relationships that they themselves have built," he said.
"You can't simply go pick up five or 10 more of these guys. They may be the best guys in the world at what they do and they're gone," he said.
Rice said it was possible that the base let its guard down in searching the bomber, who may have been coveted as an informant.
Seven CIA employees died and another six were injured, with their lives saved by US military doctors and nurses, CIA director Leon Panetta said.
It was the deadliest single incident for the CIA since 1983, when eight agency employees were believed to be among the dead when Islamic militants bombed the US Marine barracks in Beirut, killing 241 Americans and 58 French.
The attack comes as the United States increasingly relies on the CIA and other covert forces to pursue strategic goals. CIA and special forces were at the forefront of the US invasion of Afghanistan after the September 11 attacks, paving the way to overthrow the Taliban's extremist regime.
More recently -- and controversially -- the CIA has been operating unmanned drones that target extremists in lawless areas of Pakistan.
Intelligence operatives are also seen as crucial in laying out the groundwork as Obama and NATO allies send in another 36,800 troops as part of a surge expected to last until late 2010.
Thomas M. Sanderson, a scholar at the Center for Strategic and International Studies who has studied terrorist groups for the US intelligence community, said the attack could alter the mindset of operatives on the ground.
"It's highly problematic because it just makes everyone there be very suspicious of every Afghan who comes their way. Trust is going to take a hit," Sanderson said.
The killings come days after US intelligence suffered an embarrassment at home when a 23-year-old Nigerian, whose father had voiced concern about his radicalism, was allowed to board a US-bound plane which he allegedly tried to blow up.