Purpose Circulating microRNAs represent a reservoir for biomarker discovery. Our objective was to profile the change in human circulating microRNA associated with recreational use of alcohol at a social event. Material and methods Blood was collected from healthy volunteers (N=16) before and after recreational consumption of alcohol (ethanol). Biochemistry, haematology and ethanol measurements were performed. The change in the serum small RNA fraction was quantified by RNA sequencing. Results Blood ethanol was undetectable at study entry in all subjects [<10mg/dL]. After consuming alcohol the median concentration was 89mg/dL [IQR: 71-138. Min-max 20-175]. There were no changes in biochemistry and haematology parameters. Serum RNA sequencing identified 1371 small RNA species (1305 microRNAs). There were significant increases [adjusted P-value <0.05, fold increase 2 or more] in 265 microRNAs, around a fifth of the total [median fold increase 2.3 [IQR: 2.1–2.5; Max: 3.7]]. miR-185-5p decreased following alcohol exposure [adjusted P-value <0.05, fold decrease 2 or more]. Conclusions The microRNA composition of human serum is dynamic and environmental factors may have a significant impact. Within its context of use the fold change ‘signal’ of a microRNA must be large enough to negate the risk of false results due to background ‘noise’.