Fat embolism syndrome (FES) is a rare complication that can occur between 12 and 72 h after the initial insult. Isolated cerebral FES without pulmonary symptoms is rarer. Early fracture fixation might prevent FES. We report a case of multiple-fracture with FES despite definite fixation three hours post-injury.A 54-year-old man presented with multiple fractures: left femoral shaft (AO B2), left distal radius (AO C3), left comminuted patella, right comminuted 1st metatarsal base and left 2nd-4th metatarsal neck. Because he was stable, we gave him early total care and definite fixation, which required seven hours and yielded no complications. After he recovered from anesthesia, however, his eyes deviated right, his right upper arm was paralyzed, his consciousness level was poor, and his Glasgow Coma Scale score was E3VeM4. Chest X-rays showed clear lung fields, and brain computed tomography showed no intracranial hemorrhage. He did, however, have tachycardia, anemia, and thrombocytopenia. Brain magnetic resonance images showed a hyperintensive starfield pattern on diffuse weighted images, which suggested cerebral FES. After supportive care, his consciousness cleared on postoperative day 17, and he recovered full right upper arm muscle power after four months; however, he had a significant cognitive deficit. One-year post-injury, after regular rehabilitation therapy, he was able to independently perform his activities of daily living but still had a residual mild cognitive deficit.Early fixation can attenuate but not eliminate the incidence of FES. Early assessment and rehabilitation therapy might be required for patients with cerebral FES and cognitive deficits; however, such deficits are difficult to predict and need long-term follow-ups.