A case of periorbital and eyelid edema in an eighteen-year-old student is presented as the initial manifestation of acute infectious mononucleosis occurring one week before the typical prodrome. Although periorbital and eyelid edema have been reported in about 50 percent of patients with early infectious mononucleosis, its occurrence is much less frequent in clinical practice. Physicians, particularly those specializing in the treatment of cutaneous and ocular diseases, should now include acute infectious mononucleosis in the differential diagnosis of periorbital and eyelid edema.