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Economic loss due to Enterocytozoon hepatopenaei (EHP), white spot syndrome virus (WSSV) infections and other diseases to Penaeus vannamei farming in India was estimated through a questionnaire-based survey of shrimp farms in major shrimp farming states of India during 2018–2019. The survey covered an area of 7259 ha of shrimp farming in 23 coastal districts based on multistage stratified sampling (n = 909). Probability of disease occurrence (PDO) was calculated to estimate the economic loss due to diseases. Double log regression was employed to examine the relationship between economic loss with production, stocking density, culture period, average body weight, survival, FCR and incidence of disease. Loss of production (t ha−1crop−1) was highest in infections due to WSSV (2.58 ± 0.32), followed by EHP (1.80 ± 0.24), mixed infections of EHP and WSSV (1.89 ± 0.53), vibriosis (0.97 ± 0.42), running mortality syndrome (1.1 ± 0.39) and other diseases (1.72 ± 0.36). Although WSSV caused the highest loss of production (t ha−1 crop−1), EHP with a 17% probability of occurrence, accounted for a production loss of 0.77 M tons, with a corresponding revenue loss of Rs. 3977 crores (US$ 567.62 M). Although the probability of occurrence of WSSV was estimated (25%) to be higher than that of EHP, the estimated production loss due to WSSV was lower, 0.33 M tons, with a corresponding revenue loss of Rs. 1670 crores (US$ 238.33 M). National loss of revenue due to EHP was higher primarily because, in Andhra Pradesh, primary shrimp farming state had the PDO of 22% for EHP against 8% for WSSV. The total employment loss due to diseases was estimated to be 1.65 M man-days worth US$ 7.07 M. The study revealed that the overall probability of infectious disease occurrence in the country was at 49% leading to an annual loss of 0.21 M ton shrimp worth US$ 1.02 B. Economic loss due to shrimp diseases in Indian shrimp farming warrants prioritized implementation of better management practices (BMP) and biosecurity protocols along with policy interventions to reduce the direct and indirect losses.