NATO did not confirm the nationalities of the soldiers, but correspondents say US troops operate in the area.
The Taliban claimed the attack, which also killed 10 civilians, six police and an Afghan interpreter for NATO.
Witnesses said the attacker waited for the soldiers to leave their vehicles before detonating the bomb.
About 60 people were wounded in the attack, some critically.
“A suicide bomber on a motorcycle targeted a joint patrol in Khost city in a crowded area,” the governor’s office said.
Khost, like other parts of eastern Afghanistan, has seen a dramatic rise in violence.
In June, a suicide bomber killed 21 people including three US troops and a local interpreter in the city.
The Taliban-affiliated Haqqani network regularly mount large-scale attacks and suicide bombings in the area.
Over the weekend, a shooting at a checkpoint in eastern Afghanistan took the US military’s death toll in the war past 2,000.
Three US soldiers and contractor were killed in the attack in Wardak province on Saturday, along with three Afghan soldiers.
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