Central nervous system (CNS) infections are rare diseases that are associated with considerable morbidity and mortality. Increased knowledge based on contemporary data is a prerequisite for improved management and prevention of these serious conditions. Yet, population-based databases of patients hospitalized with CNS infections remain scarce. The Danish Study Group of Infections of the Brain (DASGIB) has prospectively registered information on all adults ≥18 years of age admitted with CNS infections at departments of infectious diseases in Denmark since 2015. The main variables collected are baseline demographics, blood and cerebrospinal fluid tests, imaging results, and outcome using the Glasgow Outcome Scale score. To investigate important aspects for each type of CNS infections, additional variables are included specifically for bacterial meningitis, viral meningitis, encephalitis, brain abscess, neurosyphilis, and Lyme neuroborreliosis. From 2015 to 2020, a total of 3579 cases of CNS infections have been recorded in the DASGIB database. Using the unique civil registration number assigned to all Danish residents, the database can be unambiguously linked with nationwide healthcare registries at the individual level. This enables researchers to conduct detailed population-based and longitudinal observational studies of risk and prognosis of CNS infections and to compare them with matched population cohorts. The database is well-suited for epidemiological research and the DASGIB network forms a solid infrastructure for future national and international collaborations.