Objective: To identify the serological epidemiology of Cryptosporidium infections and to follow up on the changes in the infection profile in South Egypt in order to establish a suitable scheme for control and prevention of cryptosporidiosis. Methods: A total of 1912 (960 from human and 952 from animals) stool specimens and sera were screened for Cryptosporidium species using modified Ziehl Neelsen technique and a newly-developed enzyme-linked immunosorbent assay (ELISA). Environmental risk factors and socioeconomic data were surveyed by questionnaire between September 2016 and December 2017. Results: Totally, 20.83％ of the human subjects were positive for Cryptosporidium infection tested by ELISA. The seropositivity was positively correlated with age. The prevalence of Cryptosporidium infections in females was significantly higher than in males (P<0.05). The sensitivity and specificity of ELISA for Cryptosporidium were 99.06％ and 88.88％, respectively. Furthermore, a high prevalence of Cryptosporidium in domestic animals (42.20％). Conclusions: The study observed that Cryptosporidium infections are common in the study area, with water sanitation, socioeconomic level; eating habits and hygienic status are considered the main risk factors for cryptosporidiosis. Therefore, environmental sanitation and health education will be useful in reducing the prevalence of infection.