Purpose To compare the clinical profile of COVID-related and non-COVID-related rhino-orbito-cerebral invasive fungal disease. Methods We have compared the comorbidities, clinical features, course of the disease and outcome between COVID-related and non-COVID-related acute invasive fungal rhinosinusitis (AIFRS) of the rhino-orbito-cerebral form. Results HbA1c and blood sugar at the time of admission were significantly higher in the non-COVID group ( P < 0.05). Duration of stay, and use of steroids were significantly higher among the COVID group ( P < 0.05). The period of hospital stay was significantly higher in the COVID group. The overall survival in the COVID group was 67.57%. In the non-COVID group the overall survival was 61.90%.This study found that odds of surgical treatment was significantly lower among non-survivors ( P < 0.05). Similarly patients who developed stages 3 & 4 of the disease had a lower survival rate ( P < 0.05). Conclusion Diabetes mellitus is a key risk factor for the development of AIFRS. Pre-existing, grossly uncontrolled DM was the predisposing factor in the non-COVID group. Deranged glucose profile associated with COVID illness and its treatment and immunological disturbances in a vulnerable population, contributed to the surge in cases of AIFRS in the COVID-19-related group. Patients who underwent combined medical and surgical treatment had a significantly better outcome following AIFRS.