Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection causes the disease known as coronavirus disease that started in Wuhan (China) in December 2019, leading to the current COVID-19 pandemic. The common presenting symptoms include fever, dry cough, shortness-of-breath, while sore throat, diarrhea, and abdominal and chest pain are the least. The atypical presentation of SARS CoV-2 infection poses a challenge for family physicians to screen and manage such patients for COVID-19 and specifically those at high risk with underlying disease such a sickle cell disease. Herein, we report a case of SARS CoV-2 infection in a known patient of sickle cell disease (SCD) with an atypical presentation, in whom the course of the disease was mild to moderate, uncomplicated, and the patient had an uneventful recovery. Primary care physicians should be vigilant to screen and manage such patients with established protocols, especially in the ongoing COVID-19 pandemic.