Two NATO rockets missed their targets and killed 12 civilians, during the joint Afghan and foreign military offensive against the Taliban in southern Afghanistan.
NATO said the rockets landed on a compound as troops came under fire in the Nad Ali district of Helmand province.
The office of President Hamid Karzai said the president has ordered an investigation into the civilian deaths. NATO commander General Stanley McChrystal apologised for the deaths.
They were the first reported civilian casualties since launch on Saturday of Operation Mushtarak, which is testing a new US-led war strategy aimed at re-establishing government control over the area.
US Marines are leading 15,000 US, NATO and Afghan troops in the assault focused on Marjah town, in the central Helmand River valley, which has been controlled by Taliban and drug traffickers for years.
The BBC reports it is the biggest coalition attack since the Taliban fell in 2001, and the first big test of US President Barack Obama's new "surge" strategy for Afghanistan.
This year, an extra 30,000 US troops and 10,000 from NATO are being deployed to Afghanistan.