Fat embolism syndrome (FES) is known to be relatively common in cases of multiple traumatic fractures; it is rare in cases of total knee arthroplasty. We describe a case of a 61-year-old female who underwent unilateral total knee arthroplasty, 5 hours later she developed slurring of speech, disorientation subsequently desaturated, requiring intubation. The clinical diagnosis of fat embolism syndrome was made by criteria of exclusion. Fat embolism syndrome can occur unexpectedly in elective reconstructive orthopedic procedures. One should have a high degree of clinical suspicion of fat embolism syndrome when a patient deteriorates perioperatively. The treatment is primarily supportive.