Plasma extracellular vesicles (EVs) and their cargo represent a vital source of molecular information about health and disease states and may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity-associated low type-2 asthma. Ten obese (OA) and ten non-obese low type-2 asthma (NOA) patients were selected from an asthma cohort alongside with ten healthy controls. Plasma EVs were isolated and characterised by nanoparticle tracking analysis, EV-associated small RNAs were extracted, sequenced and bioinformatically analysed. Based on EV miRNA expression profiles a clear distinction could be established between the three study groups by a principal component analysis. An integrative pathway analysis of potential target genes of the differentially present miRNAs revealed inflammatory cytokine (e.g., interleukin-6, transforming growth factor-beta, interferons) and metabolic factors (e.g., insulin, leptin) signalling pathways to be specifically associated with OA. The miR-17~92 and miR-106a~363 clusters were significantly enriched only in OA. These miRNA clusters exhibited discrete bivariate correlations with several key laboratory and lung function parameters. Further, plasma EVs miRNA signatures mirrored blood-derived CD4+ T-cells transcriptome data with even higher sensitivity in identifying specifically affected biological pathways. Thus, the identified plasma EV miRNA signatures and particularly the mentioned miRNA clusters were specifically linked to pathomechanims of obesity-associated low type-2 asthma.