Isospora belli infection, characterized by peripheral blood eosinophilia, is often seen as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). It is also reported in patients with underlying lymphoproliferative disorders including lymphoma and leukemia. Eosinophil-associated gastrointestinal disorders (EGID), including eosinophilic gastroenteritis (EGE), is characterized by eosinophilic infiltration of the gastrointestinal (GI) tract with various GI symptoms. We report a case of a 50-year-old male who developed Isospora superinfection of the small bowel while receiving systemic corticosteroids for EGE. He presented with worsening diarrhea, abdominal pain, nausea and vomiting with worsening peripheral eosinophilia. I. belli infection was diagnosed by the detection of oocysts in stool samples and by the presence of the parasite on duodenal biopsy in the background of tissue eosinophilia. I. belli can cause severe chronic diarrhea in immunocompromised patients on corticosteroids. Trimethoprim–sulfamethoxazole often provided rapid cure. Even though peripheral blood eosinophilia was seen in both EGE and Isospora infection, the identification of subnuclear protozoal inclusions as a new histologic finding, as well as the absence of this finding in previous duodenal biopsies coupled with the continued presence of tissue eosinophilia, favored a parasitic superinfection in the setting of underlying EGE.