The burden of encephalitis and its associated viral etiology is poorly described in Africa. Moreover, neurological manifestations of COVID-19 are increasingly reported in many countries, but less so in Africa. Our prospective study aimed to characterize the main viral etiologies of patients hospitalized for encephalitis in two hospitals in Dakar. From January to December 2021, all adult patients that met the inclusion criteria for clinical infectious encephalitis were enrolled. Cerebrospinal fluids, blood, and nasopharyngeal swabs were taken and tested for 27 viruses. During the study period, 122 patients were enrolled. Viral etiology was confirmed or probable in 27 patients (22.1%), with SARS-CoV-2 (n = 8), HSV-1 (n = 7), HHV-7 (n = 5), and EBV (n = 4) being the most detected viruses. Age groups 40–49 was more likely to be positive for at least one virus with an odds ratio of 7.7. The mortality was high among infected patients, with 11 (41%) deaths notified during hospitalization. Interestingly, SARS-CoV-2 was the most prevalent virus in hospitalized patients presenting with encephalitis. Our results reveal the crucial need to establish a country-wide surveillance of encephalitis in Senegal to estimate the burden of this disease in our population and implement strategies to improve care and reduce mortality.