Sickle cell disease (SCD) is the most common monogenic disorder and haemoglobinopathy worldwide and is unique in its distribution to tropical, malaria-endemic regions. SCD is typically rare in South Africa (SA) but the increasing immigration of foreign nationals over the last 20 years has the potential to alter the epidemiology of this life-threatening disease. With recent data from the Western Cape showing an increase in disease frequency, more evidence needs to be collected to determine the changes in the disease profile locally. This case series reviews the presentation and outcome of three patients diagnosed with SCD at a district hospital in Johannesburg, Gauteng.