The National Council of SPCAs has asked the health department to investigate whether "fish pedicures" pose health risks.
"As far as the NSPCA can ascertain, the treatment is not medically recognised or registered," it said in a statement on Friday.
The NSPCA's special projects unit sent a letter to Health Minister Aaron Motsoaledi and all provincial MECs on Thursday about the use of Garra Rufa or "doctor" fish in health spas.
"The issue of utilising fish at spas to 'nibble' the feet of clients and thereby undertake a pedicure has been under investigation by the NSPCA, who have concerns for the clients, as well as welfare concerns for the fish themselves."
The procedure could be risky to people with compromised immune systems, including those who were HIV positive, the NSPCA said.
In the letter to Motsoaledi, the NSPCA writes: "The concern lies with the fish that eat off of one person's skin and immediately after, another person is exposed to the same fish and water."
Health department spokesman Fidel Hadebe said he was not yet aware of the letter and knew nothing about fish pedicures or their health risks.
The NSPCA was concerned about the use of live animals in fish pedicures.
"The National Council of SPCAs have welfare and legal concerns for the fish that are being utilised, which we believe are in contravention of the Performing Animals Protection Act no 24 of 1935," the letter reads.
The NSPCA said it had issued warnings in terms of the act to several spas over welfare concerns. It called on the health department to consider regulating or banning the practice.
"We believe this industry should be regulated or stopped in conjunction with this legislation to ensure that public health and safety is taken into consideration by the spa operators."
The NSPCA said 14 US states had banned the use of the fish in spas. The UK had also taken a step towards this ban.
The NSPCA advised people not to undergo fish pedicures until the health department reported back, and those spas offering the treatment were found to be compliant with all legislation, including the Performing Animals Protection Act.
Two magisterial districts were evaluating applications from spas under the act. The magistrates had referred the issue to the NSPCA.