Pathological features of ophthalmic aftereffects of COVID-19 are important for new insight in treating patients. To examine the expression of SARS-CoV-2 nucleocapsid protein and angiotensin-converting enzyme 2 (ACE2) in lacrimal gland tissues of a patient with COVID-19 and a patient without COVID-19. In this retrospective case-control study, the case of a 35-year-old woman with positive test results for SARS-CoV-2 who had had lacrimal gland enlargements for 6 months was analyzed. A 43-year-old woman without COVID-19 who had idiopathic chronic bilateral dacryoadenitis served as a negative control. Histopathology and immunohistochemistry with anti-SARS-CoV-2 nucleocapsid protein and ACE2 in the lacrimal glands. Both patients were Japanese women aged 35 years (case) and 43 years (control). Histopathologic findings in the patient with COVID-19 demonstrated marked inflammatory cell infiltration, lymphoid follicles, and germinal center formation in the lacrimal gland. The inflammation was mainly made up of lymphocytes and plasma cells with several polymorphonuclear leukocytes, where the lacrimal glands were atrophic. Of note, a number of lacrimal gland ducts markedly contained eosinophilic materials in the lumens, which indicated glandular damage. Immunoreactivity for SARS-CoV-2 nucleocapsid protein was noted in the inflammatory cells around the lacrimal gland ductal epithelia. In addition, strong ACE2 expression was noted in the lacrimal gland. In the patient without COVID-19, marked inflammation was noted in the lacrimal gland; however, there were no eosinophilic material deposits in the ductal lumens. SARS-CoV-2 nucleocapsid protein immunoreactivity was not observed, whereas ACE2 was expressed in the lacrimal glands. In this case-control study, expression of ACE2 indicated that the lacrimal gland could be a target organ for SARS-CoV-2 to adhere to. Chronic bilateral dacryoadenitis in the patient with COVID-19 showed SARS-CoV-2-positive inflammatory cells with glandular damage, which might be a COVID-19-associated ophthalmic aftereffect.