ObjectivesTo compare the circulating microRNA (miRNA) expression profiles between sudden sensory neural hearing loss (SSNHL) patients and age‐matched normal hearing controls.Study DesignProspective cohort multi‐center study.MethodsPatients presenting within 28 days of onset of SSNHL were prospectively recruited along with contemporaneous age‐matched controls. Pooled sera of four patient (n = 09, mean age = 53.0 years; 07, 55.0; 10, 52.9; 10, 51.6) and two control (09, 51.2 and 03, 50.0) groups were assessed using a TaqMan Low Density Array. The patients’ sera were also divided into two pools, untreated (04, 57.7) and treated (32, 52.6) for additional analysis. miRNA expression level was derived from cycle threshold (Ct) values normalized to a global mean. Inter‐group mean Ct differences with fold changes ≥2.0 and ≤0.5 atP < .05 were considered significant. Bioinformatic databases were used to identify putative target mRNAs or validated genes and their functional annotations.ResultsThirty‐six SSNHL patients (mean age 53.0 ± standard deviation (SD) 15.2 years) and 12 controls (50.9 ± 11.9) were studied. Eight miRNAs hsa‐miR‐590‐5p/ ‐186‐5p/ ‐195‐5p/ ‐140‐3p/ ‐128‐3p/ ‐132‐3p/ ‐375‐3p, and ‐30a‐3p were identified as significantly differentially expressed in SSNHL patients. Most of these miRNAs were abundantly identified in the nervous system and the putative target messenger RNAs (mRNAs) were enriched in signaling pathways such as phosphatidyl inositol 3 kinase/protein Kinase B (PI3K/Akt), Ras and mitogen‐activated protein kinase (MAPK).ConclusionThese findings suggest the possible cellular signaling pathways that underlie the disruption of auditory signal transmission in SSNHL.Level of Evidence2Laryngoscope, 130:E416–E422, 2020