A suicide blast tore through the main mosque in Lashkar Gah, the capital of the insurgency-wracked province, after men had gathered for afternoon prayers, police said.
"Six people praying, including the deputy provincial governor Haji Pir Mohammad, were martyred and 18 others were wounded," Helmand province police Chief Mohammad Hussain Andiwal told the Agence France-Presse.
A spokesman for the Taliban, Zabihullah Mujahed, said that the attack was carried out by one of the group's men and it was aimed at the deputy governor.
In another incident, a bomb detonated in Kabul as an Afghan National Army bus was passing. The officers inside the bus were unharmed, but one civilian was killed and two others were wounded, Interior Ministry spokesman Zemaray Bashary told the International Herald-Tribune.
The suicide bomber, who was in a car, likely blew himself up before reaching his target, a police official said.
Buses carrying army and police personnel are a favored Taliban target with at least 65 killed in four such previous attacks in the capital since June.
"The army bus was passing from here when the explosion occurred. It looked like the whole place caught fire. Pieces of metal were flying. I saw one man on bicycle got hurt and policemen put him on an ambulance," witness Sayed Tahir told Reuters.
Afghan President Hamid Karzai condemned both attacks, saying in a statement that "the enemies of Afghanistan" had showed how weak they were by targeting people in mosques or civilians in the street.
Taliban guerrillas launched more than 140 suicide bomb attacks in Afghanistan last year, the highest since the U.S.-led military toppled the Islamic group's government in 2001.
Last year was Afghanistan's deadliest since 2001, with more than 6,500 people -- mostly insurgents -- killed as a result of violence, according to the Associated Press' count using figures provided by local and international officials.
On Wednesday in eastern Nuristan province, militants beheaded four road construction workers and dumped their bodies on the side of the road, said deputy provincial police Chief Mohammad Daoud Nadim.
The four were kidnapped 10 days ago while working on a road project in Kamdesh district, he said.
Meanwhile, a report issued Wednesday from the independent Afghanistan Study Group, chaired by former NATO commander and retired Marine Gen. James Jones and former U.S. ambassador to the United Nations Thomas Pickering, said Afghanistan risks becoming a failed state if steps are not taken to tackle deteriorating security and lackluster reconstruction and governance efforts.