The bomber eluded security at the facility -- used by the CIA as an operations and surveillance center -- in the eastern province of Khost before detonating his explosives in what U.S. officials described as a fitness center, The Washington Post reported.
U.S. military officials and diplomats confirmed the attack on Forward Operating Base Chapman near the Afghanistan-Pakistan border and the deaths.
"We mourn the loss of life in this attack," U.S. State Department spokesman Ian Kelly said.
At least one Afghan citizen died in the blast, sources said.
Eight people were wounded, several seriously, in the explosion, officials said. Several sources confirmed to the Post the deceased and wounded were civilians, adding that most likely were CIA employees or contractors.
"It is the nightmare we've been anticipating since we went into Afghanistan and Iraq," John McLaughlin, a former CIA official, told the Post. "Our people are often out on the front line, without adequate force protection, and they put their lives quite literally in jeopardy."