The Guard issued a statement saying a vehicle loaded with explosives targeted a bus carrying border guards affiliated with its force.
A video posted by Fars showed blood and debris at the site of the attack on the road between the cities of Zahedan and Khash, a volatile area near the Pakistan border.
The Fars news agency said the attack was claimed by Jaish al-Adl, a jihadist group formed in 2012 as a successor to the Sunni extremist group Jundallah, which had waged a deadly insurgency against Iranian targets. In 2009, more than 40 people, including six Guard commanders, were killed in a suicide attack by extremists in Sistan and Baluchistan province. At least 18 people were killed and more than 50 wounded.
The attack comes on the day a US-led conference takes place in Warsaw that included talks on what the Americans describe as Iran's malign influence across the Middle East.
Last month, Jaish al-Adl claimed responsibility for a double bombing in Zahedan, the provincial capital.
In December a suicide bombing in the port city of Chabahar, also in the province, killed two police officers and wounded 42 people.
"We are not waiting until there becomes a battle in Saudi Arabia, so we will work so that it becomes a battle for them in Iran and not in Saudi Arabia", he said then.
Iranian Foreign Minister Mohammad Javad Zarif appeared to blame the United States for the attack, citing a USA -sponsored conference in Warsaw aimed at rallying support to further isolate Iran.
"Is it no coincidence that Iran is hit by terror on the very day that #WarsawCircus begins?" President Donald Trump, who campaigned on a promise of tearing up Tehran's nuclear deal with world powers, withdrew the USA from the accord last May.
A meeting sponsored by the USA and held in Poland this week aims in part to build support for American efforts to thwart Iranian influence in the Middle East. Zarif wrote on Twitter.
The group, which is based in Pakistan, opposes the government in Tehran and has in the past carried out successful attacks against Iranian troops, including kidnappings, and an April 2017 ambush on the Pakistan border that killed nine border guards.