<p>Coronavirus disease (COVID-19) and diabetic ketoacidosis (DKA) are worldwide public health concerns. They are both associated with inflammation, osmotic diuresis and vascular endothelial damage. The co-occurrence of DKA and COVID-19 has few probable explanations and unknown mechanisms that result in high mortality. This perspective aims to understand the molecular downstream effects of this comorbidity and possible therapy in managing this condition. The co-occurrence of DKA and COVID-19 increases the permeability of proinflammatory products in the interstitial and vascular spaces, resulting in lung damage and fibrosis, acute respiratory distress syndrome, thromboembolism, cardiovascular and respiratory events. Entry of SARS-CoV-2 and virus complex endocytosis in the β-islet downregulates angiotensin-converting enzyme-2, propagates islet destruction, impedes insulin secretion, increases angiotensin 2 concentration causing local inflammation, apoptosis, and hyperglycaemia. These molecular changes further precipitate DKA in diabetic patients or induce it in nondiabetic patients by triggering complete insulinopenia. When comorbidity of DKA and COVID-19 is presented, treatment protocol minimises the spread of infection while maintaining glucose, fluid, pH and electrolyte homeostasis. The treatment protocol may be centred around fluid and electrolyte resuscitation, insulin treatment, low molecular weight heparin prophylaxis dosing, corticosteroids, antivirals and immunomodulatory drugs. In conclusion, proper fluid management, glucose monitoring, inflammation management, and SARS-CoV-2 infection minimisation are important in patients presenting DKA and COVID-19 comorbidity to minimise the mortality rate.</p>