UNLABELLED: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including sleep disorders. The aim of this study is to address the involvement of miRNAs (miR-21 and miR-29) in the pathophysiology of obstructive sleep apnea (OSA). In this study we have done integrated analysis of miRNAs with their potential gene targets as a strategy for management of OSA. METHODS: miRNA expression levels were quantified in healthy control group and obese vs. Non-obese OSA subjects by Quantitative real-time PCR. In-silico analysis of interplay of miRNAs with potential gene targets was done using Schrödinger Release 2023-1. RESULTS: The real time expression analysis revealed a differential expression pattern in miRNAs indicating down-regulation of miR-21 in obese OSA while miR-29 showed upregulation as compared to non-obese OSA and healthy subjects with p values of ≤0.01 and <
0.0001respectively. A trend was observed where target genes TGFBR2, NAMPT, and NPPB were significantly increased with p-value of ≤0.0001 and TGFBR3 and INSIG2 showed decreasing trend with p-value of ≤0.0001 between obese and non-obese OSA respectively. MD simulation analysis provided valuable information regarding the stability, flexibility, compactness and solvent exposure of the complexes over time. CONCLUSION: miR-21 and miR-29 possesses differential expressions in obese OSA subject and exihbits strong molecular interactions with potential target genes, such as TGFBR2, NPPB, NAMPT and INSIG2. Identifying the miRNAs, genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment.