We report a case of a 45-year-old male who presented with a headache, fever, vomiting, somnolence, and difficulty walking for 10 days. His cerebrospinal fluid studies revealed cryptococcal meningitis. Chest and abdominal computed tomography (CT) scans showed splenomegaly along with mediastinal, retroperitoneal and inguinal lymphadenopathy. CD4 count turned out to be 208 μL-1. Human immunodeficiency virus (HIV) testing, serum protein electrophoresis, serum light chains and quantitative immunoglobulins were non-diagnostic and CD4 lymphopenia was attributed to acute infection. However, a persistent CD4 lymphopenia was seen in subsequent outpatient testing, which prompted a detailed workup for secondary causes of immunodeficiency. Repeated lymph node biopsies with analytic cytometric immunophenotypic analysis were normal, as was the bone marrow biopsy with detailed immunophenotypic and cytogenetic studies. The patient was hence being treated as a case of idiopathic CD4 lymphocytopenia.