Four of the victims died in a single blast, NATO said in a statement without specifying nationalities nor providing further details. A fifth service member was killed in a separate attack in the south, NATO said.
U.S. officials confirmed all five were Americans. The officials spoke on condition of anonymity under rules regarding casualty identification.
The latest deaths bring to 75 the number of international troops killed in Afghanistan this month, including 56 Americans.
The U.S.-led force is ramping up operations against the Taliban in their southern strongholds, hoping to enable the Afghan government to expand its control in the volatile region.
Rising casualty tolls, however, are eroding support for the war even as President Barack Obama has send thousands of reinforcements to try to turn back the Taliban.
On Tuesday, an international conference in Kabul endorsed President Hamid Karzai's plan for Afghan security forces to assume responsibility for protecting the country by the end of 2014. Obama has pledged to begin removing U.S. troops starting in July 2011, although he has linked the drawdown to security conditions on the ground.
In the eastern province of Khost, a candidate in upcoming parliamentary elections died late Friday of wounds suffered when a bomb exploded earlier in the day in a mosque in the Mando Zayi district, according to local health director Dr. Amir Pacha.
The candidate, Maulvi Saydullah, was making a speech inside the mosque when the blast went off. His bodyguards and at least 15 other civilians were also hurt, officials said.
Afghanistan is due to hold national parliamentary elections Sept. 18 despite fears that they could provoke a surge in Taliban attacks.
Also Saturday, the Afghan Interior Ministry reported that five Afghan civilians were killed by a bomb in the Chora district of Uruzgan province. A total of seven militants died in clashes with Afghan and international forces since Friday night in the provinces of Khost, Uruzgan and Kunar, the ministry added without giving further details.
Four suspected insurgents were captured in two raids late Friday on Taliban hide-outs in Baghlan province of northern Afghanistan, NATO said.