Objective: The aim of the present case–control study was to evaluate the morphological aspects of the epithelial cells from the dorsum of the tongue and the expression of the SARS-CoV- 2 Spike protein in these cells, in patients with and without COVID-19 infection. Methods: 24 individuals with at least one symptom of COVID-19 were recruited among inpatients from Hospital Universitário Pedro Ernesto (Rio de Janeiro, Brazil). 14 patients who tested positive for COVID-19 by RT-PCR were included in the case group, and 10 patients who tested negative were included in the control group. Cytological smears from the dorsum of the tongue were obtained from all patients and analyzed using immunohistochemistry directed against SARS-CoV- 2- Spike protein. Morphological changes in epithelial cells were analyzed using light microscopy. Results: Immunohistochemistry showed that 71% of the COVID-19 patients presented epithelial cells positive for the presence of the SARS-CoV- 2 Spike protein, and all cells coming from patients in the control group were negative. Cytological analysis showed significant differences when comparing epithelial cells from COVID-19- positive and COVID-19- negative patients. Conclusion: COVID-19 may generate dimensional changes in tongue epithelial cells; however, further studies are necessary to understand how this happens.