The main pathological effects of COVID-19 infection have been reported to occur in the lungs, with the most pronounced manifestation being reported as Adult Respiratory Distress Syndrome (ARDS) with thromboembolic phenomena. Sickle Cell Disease (SCD) is a common genetic disorder present in 2% of newborns in Ghana. The complications of SCD include Vaso-Occlusive Crisis and Acute Chest Syndrome, which primarily manifest in the lungs. The effects of SCD on the progression of COVID-19 have not been extensively and clearly documented in literature. The objective was to describe the clinical and pathological findings in three SCD patients who died of COVID-19 related complications. A complete autopsy was performed on each of the three SCD patients who were presumed to have COVID-19. Lung swabs were subsequently taken and tested for SARS-CoV-2. The differences in histopathological findings of the three cases were highlighted and correlation with clinical findings was also done. Lung histopathological findings for all three cases were consistent with Acute Respiratory Distress Syndrome (ARDS)/ Diffuse Alveolar Damage (DAD) described for infections with COVID-19 and lung swabs tested for SARS-CoV-2 by real time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) were positive. Though SCD has been reported not to adversely affect an individual´s chance of worse outcome when infected with COVID-19, our findings suggest otherwise. We suggest that SCD may be an important co-morbidity that needs to be considered in COVID-19 patients and when present needs to be considered as an adverse risk for poor outcomes. Also, post-discharge anti-coagulation and monitoring should be encouraged. More autopsies are required to fully understand the pathogenesis of COVID-19 in SCD patients.