In Brief:
The immune reconstitution inflammatory syndrome is an exaggerated abnormal immune response, typically seen in HIV-positive patients following restoration of a normal CD4 count as a result of initiation of antiretroviral therapy. We report the case of a 60-year-old, HIV-positive African male who presented with 2 episodes of orbital inflammation that occurred in conjunction with improvements of CD4 count following Highly Active Antiretroviral Therapy. To our knowledge, this is the first case report of immune reconstitution inflammatory syndrome affecting the orbits exclusively.