Clinically relevant fat embolism syndrome (FES) is a potentially fatal intraoperative event, particularly in trauma patients. Rapid diagnosis is challenging in the perioperative setting, but treatment requires swift intervention and multidisciplinary coordination. This case report presents a polytrauma patient undergoing pelvic ring fixation who developed refractory hypoxia secondary to suspected FES. Successful initiation of anticoagulant-free venovenous extracorporeal membrane oxygenation (ECMO) intraoperatively, without definitive diagnosis, resulted in patient survival. Given the paucity of large-scale studies detailing the efficacious use of ECMO for FES in the perioperative setting, this report serves to expand the growing understanding of treatment for this potentially catastrophic event.