Enterocytozoon hepatopenaei (EHP) is a highly contagious pathogen causing hepatopancreatic microsporidiosis in shrimp, resulting in slow growth and economic losses in aquaculture. This study examined environmental factors, shrimp health, and microorganism abundance in healthy and EHP-infected Pacific white shrimp ponds. Samples from two ponds (one healthy and one EHP-infected) across two cycles were analyzed for water physicochemical parameters (salinity, temperature, dissolved oxygen, pH, ammonium, nitrite, total organic matter, phosphate, and alkalinity), bacterial and phytoplankton abundance, Vibrio population in the shrimp body, and shrimp health indicators (hepatopancreatic lipid vacuole count, necrosis, and tubule constriction). Our analysis revealed that EHP infection was observed between days of culture (DOC) 46-60 confirmed by PCR analysis. The EHP-infected pond exhibited higher pH levels at DOC 40-60 compared to the healthy pond, along with higher nitrite concentration and alkalinity. Additionally, the EHP pond had lower phytoplankton abundance and phosphate concentration than the healthy pond. In addition, the EHP pond showed higher total bacterial count, total Vibrio count, and a higher percentage of Vibrio compared to the healthy pond. Shrimp from the EHP pond displayed a lower lipid vacuole count in the hepatopancreas, higher necrosis level in the hepatopancreas, and more hepatopancreatic tubule constrictions compared to those from the healthy pond. These findings indicated metabolic issues in the shrimp from the EHP pond, resulting in slow growth and lower production indices compared to the healthy pond. These compelling results emphasize the critical need to understand and address the impact of EHP infection on shrimp health and aquaculture productivity.