BACKGROUND: Emerging evidence indicates that peripheral immune changes occur in patients with isolated REM sleep behaviour disorder (iRBD) and may contribute to the conversion of this dream enactment disorder to a neurodegenerative synucleinopathy such as Parkinson's disease, dementia with Lewy bodies or multiple system atrophy. However, with only a limited number of studies conducted, the extent to which immune changes occur across diverse iRBD cohorts remains to be determined. OBJECTIVES: We therefore aimed to assess peripheral immune changes in an Australian cohort of iRBD patients (n = 65) compared to controls (n = 35). METHODS: A 9-plex cytokine assay was used to measure serum levels of IFNγ, IL-10, IL-12, IL-17A, IL-1β, IL-2, IL-4, IL-6 and TFNα. Flow cytometry was used to assess T cell populations in the same participants. RESULTS: Exploratory analyses revealed lower levels of the T cell regulating cytokine interleukin 2 (IL-2) in participants with iRBD, along with lower frequencies of CD4 T cells positive for IL-2, IL-4 and IL-10. CONCLUSIONS: These results add to evidence of immune alterations in iRBD and suggest that dysregulation of cytokines with anti-inflammatory properties may be an early event that could associate with subsequent development of a neurodegenerative synucleinopathy.