A 12 yr old male neutered beagle was presented on transfer to the intensive care unit with severe anemia, thrombocytopenia, and bruising detected 1 day after undergoing tibial plateau leveling osteotomy surgery. The patient had undergone extra-capsular stifle stabilization surgery 14 wk prior to treat ligament disease in the same knee. Laboratory testing and treatment for anemia, presumptive immune-mediated thrombocytopenia, and possible hemostatic disorder was initiated. A persistent anemia, progressive thrombocytopenia, and the development of a firm swelling and neurologic impairment in the limb raised concerns for compartment syndrome (CS). A musculoskeletal ultrasound revealed a large aneurysm in the caudal thigh surrounded by abnormal muscle tissue. The patient underwent amputation of the limb and recovered without further complication. Pathology findings were consistent with the development of femoral CS secondary to a ruptured peripheral arterial aneurysm or a pseudoaneurysm. A consumptive thrombocytopenia and regenerative anemia were attributed to periodic or progressive thrombosis of the vessel and regional hemorrhage. Postoperative CS can develop in combination with peripheral arterial aneurysm or pseudoaneurysm, and screening for vascular abnormalities as well as CS should be considered in complicated recovery from orthopedic surgery with compatible clinical signs including progressive soft tissue swelling, persistent anemia, and thrombocytopenia.