Abstract Objectives Leukemoid Reaction (LR) signifies leukocytosis characterized by mature neutrophils. The incidence of LR is about 1 % among hospitalized patients. Mucormycosis is a rare, aggressive, fatal fungal infection that afflicts immune-compromised patients. This study discusses the case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection. Case presentation A 45-year-old female patient was presented to the hospital with confirmed SARS-CoV-2 and was given supplemental oxygen and placed on mechanical ventilation. Her skin biopsy revealed non-septate hyphae with wide-angle branching. Her blood tests also revealed the presence of LR. Conclusions Severe COVID-19 infection causes new-onset hyperglycemia, which can lead to metabolic acidosis, toxic metabolite accumulation in the body due to renal failure, the release of stress hormones and inflammatory cytokines, and the occurrence of secondary bacterial and opportunistic fungal infections. The study has shown that LR in severe COVID-19 may be associated with severe infections (bacterial or fungal) and other pathophysiological changes in the body.