Severe dengue infections are characterized by endothelial dysfunction associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and therapeutic target. The sNS1 was reported to be a hexamer with a lipid containing core based on low resolution EM data of recombinant NS1 protein. However, how the sNS1 hexamer forms and how sNS1 may cause vascular leakage remains elusive. The hexamer model is challenged by recent evidence suggesting NS1 may be associated with HDL and uses scavenger receptor B1 (SCARB1) as a cell receptor in cultured cells. To reconcile the findings of the functional forms of sNS1 and better understand its biological roles, the native form of sNS1 from cells infected with DENV are purified. We determined the cryoEM structures of sNS1 and its complex with a monoclonal antibody/Fab. The major species of sNS1 is a 1:1 complex of the NS1 dimer embedded a High-Density Lipoprotein (HDL) particle. Cross-linking MS studies confirm NS1:ApoA1 dimer formation with most ApoA1 interaction sites mapped to the NS1 wing and hydrophobic domains. These results report the molecular architecture of the secreted NS1 and provide insights on the molecular mechanisms of dengue pathogenesis.