The attack took place as men were getting ready for the evening prayer at the central mosque in Zaranj, the capital of Nimroz province, Gov. Ghulam Dastagir Azad said.
Azad said there may have been more than one bomber.
"I'm not sure if it was single attack or a double attack," he said, noting that a district police chief and border reserve police commander were among the dead.
"The reports I've received from the hospital indicate that most people are in critical condition. I'm scared the death toll will rise," he said.
At least two other suicide attacks have hit Nimroz this month, including an attack on April 1 that left two policemen dead in Zaranj, and another on Saturday that killed two Indian road construction engineers and their Afghan driver in Khash Rod district.
Suicide attacks in Afghanistan spiked last year, with the Taliban launching more than 140 such missions the highest number since the radical Islamist group was ousted from power by a U.S.-led invasion in 2001.
In central Ghazni province, militants ambushed a patrol of Afghan and foreign troops Thursday in Gilan district, and the ensuing clash left nine Taliban fighters dead, said district chief Abdul Wali Thofan. There were no casualties among the troops.
A roadside bomb struck a Canadian military on Thursday near Spin Boldak, a town on the Pakistani border, said Lt. Cmdr Pierre Babinsky, a spokesman for NATO troops in the south. No one died in the blast, but he declined to say whether any soldiers were wounded.
The insurgency has left more than 1,000 people dead so far this year, most of them militants, according to an Associated Press tally of figures provided by Afghan and Western officials.
Meanwhile, NATO acknowledged that a privately contracted helicopter had mistakenly dropped ammunition and other supplies in an area where Afghan officials have said the items were picked up by the Taliban.
NATO's International Security Assistance Force said Thursday that the helicopter shipment of food, water and ammunition intended for police was mistakenly dropped in southern Zabul province. The head of Afghanistan's intelligence service, Amrullah Saleh, told a parliamentary security committee Sunday that Taliban fighters took the supplies.
The force said in a statement that the helicopter was contracted by ISAF to resupply a police outpost in a remote mountainous location in March.
"Unfortunately, due to a human error in transcribing the latitude and longitude of the location, the load was dropped in another remote area," said the ISAF statement, which did not mention whether the supplies reached the insurgents.
"The mistake was recognized when the helicopter crew was debriefed after returning to their base. Coalition forces sent aircraft for a visual reconnaissance, however, the missing cargo could not be found."