Nato has acknowledged the incident, without detailing how many Afghans died, and promised an investigation.
The US air strikes are part of a Nato mission to support Afghan forces against the Taliban.
The latest incident took place on Friday afternoon in the Gereshk district.
"In the strike, 16 Afghan policemen were killed including two commanders. Two other policemen were wounded," Helmand police spokesman Salam Afghan told AFP.
A Nato statement said: "During a US-supported (Afghan security) operation, aerial fires resulted in the deaths of the friendly Afghan forces who were gathered in a compound.
"We would like to express our deepest condolences to the families affected by this unfortunate incident."
In a separate development, there are reports of numerous casualties after the Taliban ambushed an Afghan police patrol in the north-eastern Badakhshan province.
Some reports say at least 10 police officers were killed, while local officials put the figure at 35.
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