The novel coronavirus (COVID-19) pandemic has stretched the medical resources of both developed and developing countries. The global focus on COVID-19 may lead to the neglect of other infectious diseases such as malaria which is still endemic in many African countries. Some similarities in malaria and COVID-19 disease presentations may also lead to late diagnosis of either disease which could complicate the effects. Here, we present two cases of a 6-year-old child and a 17-year-old female who presented to a primary care facility in Ghana with a clinical and microscopy-confirmed diagnosis of severe malaria complicated by thrombocytopenia. As their symptoms worsened with associated respiratory complications, nasopharyngeal samples were taken for real-time polymerase chain reaction (RT-PCR) and tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinicians, policymakers, and public health practitioners should be alert to the variety of presenting symptoms of COVID-19 and its similarity to malaria to mitigate the risk of mortality from either disease.