An Afghan provincial police official, Colonel Yaqub, said the blast was a suicide attack on an ISAF patrol in the city of Khost and that several civilians had also been killed.
An ISAF spokesman said he could confirm that three NATO troops had been killed but that details of the incident were still unclear.
NATO has more than 100,000 troops in Afghanistan, but they are due to pull out by the end of 2014.
The latest blast came a day after NATO announced that a firefight between ISAF troops and their Afghan allies killed a U.S. soldier, a civilian contractor and three Afghan army troops in circumstances that remain unclear.
Based on reporting by dpa, AFP, and AP