The deaths, the latest in a string of civilian casualties at the hands of US forces in the past year, were likely to spark anger in a population that often views American soldiers as heavy-handed and over-aggressive.
The deaths occurred on a road in Ghazni province on Saturday night when the pickup truck ran through a joint US-Afghan military checkpoint, the military said in a statement on Sunday. Soldiers searched the pickup, but did not find any weapons.
Ghazni Governor Haji Asad Allah Khalid said the pickup was driving in the Afghan desert when it happened upon a checkpoint on the main road. He said the soldiers first fired into the air then opened fire on the truck.
"These deaths were a tragedy. It is very very sad news," Khalid said. He said he sent his deputy governor to the site to investigate and an Interior Ministry delegation was also headed to the area from the capital, Kabul, 120km to the north.
The US military said the incident was under investigation although it gave no indication any of the soldiers involved were believed to have acted improperly.
"Vehicle checkpoints play an important role in maintaining security in the area, providing security forces the opportunity to find wanted people and contraband, such as weapons, bombs and drugs," the statement said. "Vehicle occupants approaching checkpoints should stop and follow security personnel's instructions," it said.
A critically injured man and woman and an uninjured infant were evacuated to Bagram Air Base, the US military's main base in Afghanistan, for medical treatment, the statement said.
Karzai's (R) government is looking
into the deaths
Jawad al-Din, a spokesman for President Hamid Karzai, said the government was looking into the deaths and would have a statement later in the day.
On 9 August Lieutenant-General David Barno, the top US commander in Afghanistan, agreed to a 15-point plan to improve relations with Afghan civilians and officials after Karzai called him in for talks, a military spokesman said.
Local leaders have repeatedly complained of heavy-handed tactics by the US-dominated coalition, especially during searches that sometimes involve air power and take place at night.
Rights groups warn that the aggressive approach may have caused unnecessary deaths and stoked sympathy for Taliban fighters who continue to defy the currently 18,000-strong force under Barno's command.
A US air raid in Uruzgan province in January killed 11 villagers, including four children, Afghan officials charged. The US military has maintained that five "militants" were killed in the raid.
On 5 December, six children died when a wall fell on them during a nighttime assault on a complex in eastern Paktia province by the US military.
The next day, nine children were found dead in a field after an attack by an A-10 aircraft on a village in neighbouring Ghazni province.
The US military is also investigating several allegations that prisoners were abused in its jails in Afghanistan, including cases involving at least four deaths.