It has been reported that in 25% of coronavirus disease 2019 (COVID-19) cases, the central and peripheral nervous systems have been affected. Furthermore, there is an established association between COVID-19 and encephalitis, which most often presents with confusion and disorientation. The mortality rate of encephalitis can be decreased by early diagnosis and treatment. Here, we present a case of a 71-year-old woman who was hospitalized with the symptoms of confusion and fever and was found to be COVID-19 polymerase chain reaction (PCR)-positive by both cerebrospinal fluid (CSF) and nasopharyngeal swab analysis. The patient underwent transsphenoidal pituitary surgery 4 months before her admission and was in an acute confusional state accompanied with consciousness fluctuations and agitation. On magentic resonance imaging, the hyperintensities detected in the T2 and fluid-attenuated inversion recovery axial sections of the bilateral temporal brain areas and paramedian region of pons were observed to be compatible with encephalitis. The nasopharyngeal and CSF severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) PCR was performed because the thorax computed tomography revealed findings compatible with COVID-19 pneumonia and both the samples were found to be PCR-positive. Encephalitis arising from toxic and metabolic causes was excluded. In this case, the COVID-19-associated encephalitis was treated with dual antiviral (favipiravir and acyclovir) and steroid therapies. This case was considered unique as very few cases of positive nasopharyngeal and CSF SARS-CoV-2 RNA PCR have been reported and because of the patient’s history of transsphenoidal pituitary surgery 4 months before her hospitalization.