Cyanobacterial blooms drive water-quality and aquatic-ecosystem deterioration in eutrophic lakes worldwide,mainly owing to their harmful, secondary metabolites. The response of fish exposed to these cyanobacterialchemicals, however, remains largely unknown. In this paper, we employed an endangered fish species(Sinocyclocheilus grahami) in Dianchi Lake, China to evaluate the risks of cell-free exudates (MaE) produced by adominant cyanobacterium (Microcystis aeruginosa) on embryo development, as well as the molecular mechan-isms responsible. MaE (3d cultured) caused a reduction of fertilization (35.4%) and hatching (15.5%) rates, andincreased mortality rates (≤90.0%) and malformation rate (27.6%), typically accompanied by heart failure.Proteomics analysis revealed that two greatest changed proteins – protein S100A1 (over-expressed 26 timescompared with control) and myosin light chain (under-expressed 25 fold) – are closely associated with heartfunction. Further study revealed that heart failure was due to calcium ion imbalance and malformed cardiacstructure. We conclude that harmful secondary metabolites from cyanobacteria may adversely affect embryodevelopment in this endangered fish, and possibly contribute to its disappearance and unsuccessful recovery inDianchi Lake. Hazardous consequences of substances released by cyanobacteria should raise concerns formanagers addressing recovery of this and other imperiled species in affected lakes.