"We have removed yet another Taliban enemy leader who will no longer threaten the peace and security of the Afghan people and their future," Lieutenant-Colonel Angela Billings, an ISAF spokeswoman, said.
Wali Mohammad, a resident of Musa Qala, said the air strike against the compound in a small village a half hour outside Musa Qala killed 20 fighters who had sought shelter there the previous night.
Neither Nato or Afghan officials could confirm that death toll.
Violence has spiked in the southern province of Helmand the last two weeks. The governor said some 700 foreign fighters are in the region around Musa Qala and Kajaki, in the mountainous northern edge of the province.
Nato and Afghan forces killed 22 Taliban fighters in separate clashes near Musa Qala and Kajaki the last several days, officials said on Tuesday.
The government is negotiating with local elders in hopes that Taliban fighters will leave Musa Qala peacefully, though thousands of residents have fled out of fear of an impending attack by Nato and Afghan forces.
Colonel Tom Collins, a spokesman for the Nato-led force, said Western troops were waiting to see if the dispute could be resolved through negotiations but were ready for military action if the government so requested.
Also on Wednesdsay, Afghan authorities announced they had captured Mullah Daud Trabi, a senior Taliban commander who had been the Khost provinice's chief of the "vice and virtue" police that imposed the Taliban's ultra-conservative moral code during their 1996-2001 hold on power.
He was captured in the eastern city of Khost on Tuesday, the interior ministry said in a statement.
Trabi was captured while on the move between Afghanistan and "outside the border," the statement said, referring to Pakistan where US and Afghan officials say the Taliban and its al-Qaeda allies have sanctuaries.
Elsewhere in Helmand province, auxiliary police protecting a poppy-eradication team were hit by a roadside bomb on Tuesday that killed two policeman and wounded three, Eisah Mohammad, the provincial police chief, said.
Meanwhile, officials in Pakistan said on Wednesday that an attacker killed in a shootout on February 6 at the international airport for Islamabad, the nation's capital, was an Afghan-trained member of an outlawed Pakistani fighters' group.
Security forces fatally shot the man when he opened fire and tried to hurl a grenade at them after they asked him to stop in a car park near the airport's international terminal.
On Wednesday, a senior security official said investigators were sure they had identified the man. "He is a Pakistani. His name is Qari Mohammed Younus," the official said on condition of anonymity.
The official said the man was a member of an outlawed Pakistani fighters' group who had received training in Afghanistan and had fought in Indian-administered Kashmir.