This study was done in order to characterize a large series of acute infectious encephalitis and myelitis in immunocompetent patients from the Caribbean island of Guadeloupe identifying clinical, biological, and radiological features according to pathogens.

Using a hospital database, detailed information on a comprehensive series of immunocompetent patients with acute infectious myelitis and encephalitis over the 2012–2018 period was retrospectively collected.

Initially, there were 259 suspected cases with acute central nervous system infection, out of them only 171 cases were included for analysis who fulfilled the inclusion criteria. The annual incidence peaked at 15.0/100 000 during the Zika 2016 outbreak. Children accounted for 22.2% of cases. Eight adults died during a hospital stay, all encephalitis. 17 infectious agents, two of which had never been described in Guadeloupe so far, were identified in 101 cases, including 35 confirmed cases, 48 probable cases, 15 possible cases, and three clinical cases. The most frequent etiologic agents were the Zika virus in 23 cases, herpes simplex in 12, varicella-zoster virus in 11, dengue virus in 11, and leptospirosis in 11.

The findings of this study concluded that the Zika outbreak had a major influence on the annual incidence of acute central nervous system infection. Acute neuroleptospirosis is over‐represented in our series.