During months of fighting, the Taliban have seized control of large parts of Helmand and driven government forces from several districts.
In a nighttime helicopter raid, counter-terrorism operators and special forces based in the neighbouring province of Kandahar attacked the house in Naw Zad district and freed the prisoners, according to a statement from NATO's Resolute Support mission in Kabul.
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It said coalition forces supported the raid as part of their train, advise and assist mission but gave no details.
At least two insurgents were killed and several were wounded or detained.
The governor of the southern province, Hayatullah Hayat, said the prisoners released during the raid had been taken to Kandahar.
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"We are still investigating as to who these people are and how long they were kept there," he said.
The Taliban insurgency has gained strength since the withdrawal of international troops from combat at the end of 2014, with the militants stronger now than any point since they were driven from power by US-backed forces in late 2001.
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However, fighting has eased recently, partly because the annual opium harvest has meant that many fighters have been employed in the fields of Helmand, where the largest share of Afghanistan's poppies are grown.
Resolute Support spokesperson General Charles Cleveland told reporters on Thursday that commanders expect the fighting to pick up as the harvest is completed over the next few days.
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