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Acute Respiratory Distress Syndrome (ARDS) is a hyper-inflammatory lung disorder which develops following sepsis. Alveolar macrophages (AMs) from ARDS patients have impaired efferocytosis compared to control ventilated sepsis patients (PMID:34112730). This defect is replicated when healthy AMs are treated with ARDS patient broncho-alveolar lavage fluid (BAL) (PMID:34660643). Impaired AM efferocytosis contributes to alveolar inflammation via secondary necrosis of apoptotic neutrophils. Lung injury models implicate EVs in ARDS pathogenesis. We hypothesised BAL EVs drive AM dysfunction in ARDS.EVs were isolated from ARDS and post-operative control patient BAL via ultracentrifugation. AMs were isolated from lung tissue resections of non-smoking patients. AMs were treated with BAL EVs 24 hours prior to assessment of efferocytosis, Seahorse XF analysis, ICC and Western Blot. ARDS BAL EV treatment impaired AM efferocytosis (fc 0.541, p=0.0029). AMs treated with ARDS BAL EVs had increased basal OCR (p=0.0391), maximal respiration (p=0.0273) & ATP driven by mitochondrial respiration (p=0.0039). Markers of mitophagy (LAMP1 & LC3B) were decreased in AMs after ARDS EV treatment (p=0.0156 & p=0.0312). Thus, accumulation of damaged mitochondria may drive the dysfunction observed.Transcriptomics reveal enrichment of 8 microRNAs in ARDS BAL EVs. EV miR-15a & miR-26b inversely correlate with ex vivo AM efferocytosis. Transfection of healthy AMs with miR-15a & miR-26b mimics impairs efferocytosis (p=0.0115) and decreased LC3B & LAMP-1 expression, replicating the effects of EV treatment.Targeting EV microRNA cargo may attenuate AM dysfunction & inflammation, offering a therapeutic strategy for ARDS patients.