A significant disease of concern in captive populations of snakes is gastric cryptosporidiosis, caused by Cryptosporidium serpentis, a gastrointestinal, protozoal parasite that can cause varying degrees of morbidity and mortality. The purpose of this study was to understand physiological responses of eastern indigo snakes (EIS; Drymarchon couperi) infected with C. serpentis. Body condition index (BCI), heterophil:lymphocyte ratio (HLR), bactericidal ability (BA), sheep red blood cell hemolysis-hemagglutination assays (SRBC), and plasma corticosterone levels (CORT) were compared between EIS across cryptosporidiosis infection states including cryptosporidia infection positive with clinical signs, infection positive without clinical signs, infection-recovered, and infection-free snakes. We found snakes that had recovered from C. serpentis had significantly lower SRBC titers than C. serpentis–negative snakes (P < 0.05). Recovered snakes had significantly higher BCI than infection positive with clinical signs, infection positive without clinical signs, and infection-free snakes (P = 0.00198). Female EIS had significantly higher CORT levels than males (P = 0.0112), BA had a significant positive relationship with HLR (P = 0.0333), and BA had a significant relationship with SRBC (P = 0.0170). These results give meaningful insight into reptilian physiology of disease and show that snakes recovered from C. serpentis may have remaining negative effects of cryptosporidiosis on their immune system. Results from this study may aid conservation projects in determining suitability for release of EIS that have been infected with C. serpentis.