"They were on a patrol in Kabul and were attacked by an IED (improvised explosive device)," a spokesman for NATO's International Security Assistance Force (ISAF) said.
"Four were injured and two died... They were Italians," Staff Sergeant Brian Lamar said.
The six soldiers were travelling in two armoured vehicles in the south-eastern part of Kabul when they were hit by the explosion, the ANSA news agency in Rome reported, quoting the Italian contingent's command in Afghanistan.
Two died of their wounds shortly afterwards, it said.
Italy has nearly 2000 troops deployed in Afghanistan as part of the ISAF peacekeeping force, of which NATO took command in 2003.
The 10,000-strong force, drawn from around 36 countries, has been in Afghanistan since the hard line Taliban government was overthrown in late 2001.
It is based mainly in northern and western Afghanistan and in Kabul, and has been trying to stabilise the volatile nation now battling a Taliban-led insurgency.