The IRGC personnel were traveling between the cities of Zahedan and Khash, in Sistan and Baluchestan province on Wednesday, when their bus was targeted in a suicide vehicle bomb attack.
While Sunni militant groups are not regarded as a major threat, the attack dealt a fresh blow to Iran's security establishment, which has often said it can repel any threat no matter how big, even from the United States and its ally Israel.
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.
The statement does not give the exact number of the martyred soldiers and the injured.
Back in October 2018, at least 29 people were killed and 70 others wounded in an attack on a military parade in Iran's southwestern city of Ahvaz.
However, a bombing like this inside of Iran likely will draw an immediate reaction from the Guard, a massive paramilitary organization that both controls Iran's ballistic missile program and vast chunks of its economy. In September, Iran fired missiles into Iraq targeting a base of an Iranian Kurdish separatist group after an attack on a border post.
In December a suicide bombing in the port city of Chabahar, also in the province, killed two police officers and wounded 42 people.
The group's Quds Force unit said the United States, its allies and Zionism shared responsibility for the attack, without elaborating on the claim. Saudi Crown Prince Mohammed bin Salman for instance in a 2017 interview suggested the kingdom knew it was a "main target of Iran".
It came on the same day that a conference convened by the United States in Warsaw was to include discussions on what Washington describes as Iran's malign influence across the wider Middle East. There have been sporadic protests in the country as well, incidents applauded by Trump amid Washington's maximalist approach to Tehran.
Iran's foreign minister, Mohammad Javad Zarif, described the conference convened by the USA as the Warsaw Circus, and said it was "no coincidence that Iran is hit by terror on the very day" that the talks began.
The Guards issued a statement confirming the attack.
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 earlier predicted the Warsaw summit would not be productive for the U.S.