Among the symptoms of African Horse Sickness are fever, sweating, breathing difficulties, discharge from the nose, and swelling of the eyes and/or head.
Authorities have confirmed the deaths of the animals since March 16 within the African horse sickness surveillance zone, and are urging the postponement of horse events throughout the country until more is known about the disease outbreak.
The surveillance zone, which covers Cape Town and surrounding districts, must remain clear of the disease to allow South Africa's bloodstock export industry to operate.
Post mortem examinations have been conducted and "intensive" laboratory investigation is under way to determine the involvement of the disease in any or all of the deaths.
A spokesman said: "Various infectious agents able to cause disease in equines are under suspicion, including Equine Encephalosis Virus. African horse sickness virus has also not been eliminated as the cause of the current disease outbreak, whether alone or possibly in combination with other infectious organisms.
"As outbreaks of African horse sickness directly impact on the export of horses from the AHS Free Area, the real cause of these cases would have to be established to the satisfaction of the World Animal Health Organisation (OIE) and the veterinary authorities of our equine trading partner countries."
African Horse Sickness, which is carried by a midge, has a mortality rate of up to 90 per cent. There have already been outbreaks in mainland Europe and Britain is putting in place plans to cope with what authorities believe will be an eventual outbreak on its shores.
South African agricultural authorities are urging horse owners to report any fevered horses with breathing difficulties to a veterinarian.
As part of a containment strategy, a total ban is in place on the movement of horses, donkeys, mules and zebra within, into, and through the surveillance zone.
"As requested previously, all horse owners and organisers of equine shows, meetings and competitions throughout the country, are urgently requested to postpone imminent major horse gatherings until more clarity with respect to this epidemic is obtained. These are major decisions, but can in the long run, only be advantageous to the local as well as national equine industry and sporting codes."