On Monday, President Cyril Ramaphosa announced an increase of confirmed cases from 1 280 to 1 326, with a death toll of three.
The US embassy in South Africa urged its citizens who wished to return home to reach out to it.
This entails filling out a form detailing their location and personal details.
"We want to ensure that if an opportunity to return is presented, we have as complete a database as possible.
"Once specific flight details are confirmed, US citizens need to make their own way to OR Tambo International Airport in Johannesburg, Cape Town International Airport, as well as King Shaka International Airport in Durban," the embassy said.
It is currently not clear how many US citizens are in South Africa.
The US has the highest number of Covid-19 cases in the world, reaching 160 700 positive cases and more than 3 000 deaths.