Afghan authorities and NATO said they had launched a joint investigation into the deaths, which could further strain relations between President Hamid Karzai and his international allies.
According to NATO and provincial government spokesman Dawood Ahmadi, insurgents had fired at NATO troops and Afghan army and police from inside the compound in Helmand province's Nahri Sarraj district on Monday, prompting the airstrike.
The presence of the civilians -- two women, an elderly man and a child -- was discovered only after the troops entered the compound, NATO said.
Afghan and international forces have launched a joint investigation "to review the factors leading up to this unfortunate loss of civilian life," NATO said in its statement e-mailed to journalists.
Ahmadi confirmed the report and said it was possible that the casualty count could increase.
"We have already sent a delegation to investigate this incident and bring the (Helmand) governor a complete report with the exact information and figures as to how it happened, how they died, and by whom they were killed," Ahmadi said.
Civilian deaths are highly sensitive because they stir resentment against the 120,000 foreign troops in the country and could drive more Afghans into the arms of the Taliban insurgency. U.S. commanders have ordered troops not to use heavy firepower when civilians are believed to be present and avoid nighttime house searches.
Earlier this week, NATO confirmed that international troops were responsible for the deaths of five civilians, including three women, on Feb. 12 in Gardez, south of Kabul.