Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (alpha1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4-positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-gamma) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.