Acute meningitis can be the first manifestation of an underlying systemic inflammatory disorder (SID). In the current study, we aimed to identify clinical indicators for SIDs in patients admitted for acute aseptic meningitis. All patients hospitalised for acute aseptic meningitis over a 4-year period in a department of internal medicine were included retrospectively. Patients with neoplastic meningitis were excluded. Extraneurological signs were recorded using a systematic panel. Systemic inflammatory disorder diagnosis was made according to current international criteria. Forty-three (average age 46 years [range 19–82 years], 60% females) consecutive patients were analysed retrospectively. Of these, 23 patients had an SID (mostly sarcoidosis and Behçet's disease). Multiple logistic regression analysis showed that the probability of an SID was 93.7% in patients with both neurological and extraneurological signs, but 14.9% in patients with neither neurological nor extraneurological signs. In conclusion, clinical sorting according to both neurological and extraneurological signs could help to identify patients with acute aseptic meningitis caused by an SID.