Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) and one of the leading causes of mortality in SCD patients. The management of ACS is challenging and requires prompt intervention to halt clinical deterioration. With the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, which also primarily results in acute respiratory illness, the clinical picture and treatment outcome in SCD patients with ACS remain unknown. We present a case of a 30-year-old male who came in with features of painful vaso-occlusive episode and haemolysis that later evolved to acute chest syndrome. Chest X-ray showed pneumonic changes and mild bilateral pleural effusion, and nasal Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for COVID-19 test came out positive. He was managed supportively with simple transfusion, antibiotics, dexamethasone and oxygen support with a good clinical outcome. Presenting with non-specific symptoms and similar respiratory symptoms and signs, the clinical picture of COVID-19 can prove difficult to discern from that of ACS due to other causes. This report emphasizes a need for a higher index of suspicion whenever a SCD patient presents with symptoms of acute respiratory distress.