Bone marrow edema is a common and nonspecific finding on magnetic resonance imaging (MRI) and results from various diseases including infection, inflammation, neoplasm, injury, and osteoarthritis. However, bone marrow edema syndrome (BMES) represents a distinct entity with specific clinical and imaging features such as diffuse extensions, the lack of other morphologic alterations, no history of trauma, and reversible disease courses. BMES is caused by ischemic changes, and thus, it is postulated to occur as a result of the thrombosis in a patient with primary anti-phospholipid syndrome (APS). Here, we present a case of 67-year-old male with a history of stroke, being presented with fever of unknown origin and pain on both knees. He had high titers of IgG and IgM anti-cardiolipin antibodies which titers didn’t change after 3 months. He was diagnosed as having a BMES due to typical MRI findings. After the introduction of anticoagulation, fever and joint pain were subsided. Our case suggests that BMES can develop within a patient with APS, thus early detection of differentiations is essential to avoid unnecessary treatments.