"SAHPRA has been informed of a second fatal case of Guillain-Barre syndrome (GBS) following vaccination with the Covid-19 vaccine Janssen," it said in a statement, using the vaccine's commercial name.
In a response to AFP Tuesday, Johnson & Johnson said "very rare cases of the neurological disorder, Guillain-Barre Syndrome (GBS) have been reported following vaccination with the Janssen Covid-19 vaccine with most occurring during the first 42 days following vaccination".
"GBS is a very rare but severe adverse event that is associated with the administration of various vaccines and other medicines and can also be triggered by infections such as SARS-CoV-2," it said, but made no direct reference to the South African cases.
Pressed for details, SAHPRA on Tuesday refused to disclose further information, citing "patient confidentiality" rules.
The regulator added that "the events reported in the vaccine recipient were consistent with the case definition of GBS and no other likely cause of GBS was identified at the time of illness" of the latest case.
GBS is a rare neurological condition that may occur with the administration of various vaccines or bacterial and viral infections.
It damages nerve cells, causing muscle weakness, numbness, tingling or, in the most severe cases, paralysis.
South Africa has recorded more than four million Covid-19 cases and 102,129 deaths -- the highest toll in Africa.
Out of the population of around 60 million South Africans, 20.3 million individuals have been vaccinated -- more than 9.2 million of them with the J&J formula, against 12.5 million who received the Pfizer jab, according to official statistics.