Tilapia are the 3rd most cultured aquaculture species in global aquaculture, produced in over 170 countries. Bangladesh is the world's fourth-largest tilapia producer and yet only few studies have been conducted to understand factors associated with tilapia mortality and economic losses. Using an online tilapia epidemiology and health economics survey tool, we surveyed 565 tilapia farms in 15 of Bangladesh's most important tilapia-producing districts. The study examined a range of factors, including geographic locations, farm characteristics, water source, stocking, biosecurity measures, baseline and unusual mortality levels and characteristics. For the period January 2017 to February 2019 a total of 18.2% of farms (103 out of 565) reported having experienced unusual mortality, with an average mortality level of 23.2% (range 3 to 90). A number of factors were found to be significantly associated with reporting of unusual mortality occurrences, including farmer education level, farm size, farm biosecurity measures, baseline mortality level, farmer concern about baseline mortality, dead fish removal frequency and disposal method and antibiotic treatment. Farming region, water source, dead fish removal frequency, and antibiotic treatment were all found to be significantly associated with the level of unusual mortality, with water source and dead fish removal frequency remained significant in the multivariable model. Major clinical signs linked with these mortalities included skin erosions, hemorrhagic lesions, open wounds, skin discoloration, exophthalmos, abdominal distension, swelling, scale protrusion and eye opacification. Based on baseline and unusual mortality in tilapia, a total hidden loss of 875.7 million USD annually was estimated. To ensure the future sustainability of tilapia production, the authors recommend more investigations of unusual mortalities events with collection of metadata and clinical samples for disease diagnostics, coupled with nationwide farmer awareness campaigns.