Hyponatremia can occur with central nervous system (CNS) infections, but the frequency and severity may depend on the organism and nature of CNS involvement. In this cross-sectional study at a large Australian hospital network from 2015 to 2018, we aimed to determine the prevalence and severity of hyponatremia associated with CNS infection clinical syndromes, and the association with specific organisms. We examined the results of cerebrospinal fluid analysis from lumbar punctures performed in 184 adult patients with a serum sodium below 135 mmol/L who had abnormal cerebrospinal fluid analysis and a clinical syndrome consistent with an acute CNS infection (meningitis or encephalitis). Hyponatremia affected 39% of patients and was more severe and frequent in patients with encephalitis compared to meningitis (odds ratio = 3.03, 95% CI: 1.43–6.39, after adjusting for age). Hyponatremia was present on admission in 85% of cases. Herpes simplex virus infection was associated with the highest odds of hyponatremia (odds ratio = 3.25, 95% CI: 1.13–7.87) while enterovirus infection was associated with the lowest (odds ratio = 0.36, 95% CI: 0.14–0.92), compared to cases without an isolated organism. We concluded that the risk of hyponatremia may vary by the organism isolated but the clinical syndrome was a useful surrogate for predicting the probability of developing hyponatremia.