We present a rare case of multifocal Proteus mirabilis osteomyelitis in an HIV-positive patient. Despite the patient’s good immune status as assessed by her CD4 cell count and the aggressive treatment, she eventually underwent bilateral above-knee amputations to eradicate the infection. Multifocal Proteus mirabilis osteomyelitis can have an unpredictable clinical course with a severe outcome in HIV-positive patients.