British, Canadian and Dutch troops make up the bulk of Nato forces in southern Afghanistan, part of the main bastion for Taliban fighters.
The deaths on Wednesday took to 105 the number of foreign soldiers killed in Afghanistan this year, most of them in combat.
"The Isaf community mourns the loss of these brave soldiers," Lieutenant Colonel Maria Carl, an Isaf spokeswoman, said.
"They gave their lives to improve the lives of the Afghan people."
It was the deadliest explosion on the Nato forces since six Canadian soldiers were killed after a mine exploded on April 8.
Meanwhile, a German citizen has disappeared in Afghanistan, the German foreign ministry and a local Afghan official said on Wednesday.
"A German citizen is missing in Afghanistan," Martin Jaeger, a German official said. "All indications are that he's been kidnapped."
An Afghan official said the man had gone missing in the western province of Farah which borders Iran and is an area where both Taliban fighters and drug smugglers are active.