Objective— The purpose of this study was to investigate the interaction of SAA and SR-BI in remodeling of acute phase HDL (AP HDL). Methods and Results— We used SAA and SR-BI adenoviral vector expression models to study the interaction between these entities. SR-BI processing of mouse AP HDL generated progressively smaller discreet HDL particles with distinct apolipoprotein compositions. SR-BI actions segregated apolipoproteins with the smallest particles containing only apoA-I. Larger remnants contained apoA-I, apoA-II, and SAA. Small apoA-I only particles failed to associate with preformed HDL, whereas larger remnants readily did. The presence of SAA on SR-BI-processed HDL particles propelled apoA-I to a small lipid-poor form and accelerated apoA-I catabolism. Conclusions— Data indicate that after core and surface HDL lipid perturbation by SR-BI, SAA propels apoA-I to a small lipid-poor form while accelerating HDL metabolism.