Lyngbya wollei is a benthic filamentous cyanobacterium that produces a toxin analogous to the neurotoxic saxitoxin known as lyngbyatoxin (LYNGTX). Microcystis aeruginosa form blooms in the pelagic area of eutrophic lakes and produce a series of potent hepatotoxins-microcystins (MCYST). The aim of this study in vitro study was to examine the difference between the crude extracts of either M. aeruginosa or L. wollei toward the immune system of Elliptio complanata mussels. Freshly isolated hemolymph was plated and exposed to the crude extract of each species at LYNGTX or MCYST equivalent concentrations of 5, 10 and 25 μg/L for 18 h. Immunocompetence was characterized by following changes in hemocyte numbers, metabolic activity (viability), and phagocytosis. Hemocyte counts were not affected, indicating no turnover of hemocytes. Hemocyte metabolic activity was higher in cells exposed to crude extracts of L. wollei. Exposure to L. wollei extracts led to decreased pro-inflammatory precursors such as reactive oxygen species (ROS) and cyclooxygenase (COX) activities. Phagocytosis increased at 25 μg/L for both types of crude extracts. However, hemocytes exposed to crude extracts of M. aeruginosa produced more ROS and COX compared to hemocytes exposed to crude extracts of L. wollei. In conclusion, the data suggest that the crude extract of M. aeruginosa was more toxic than crude extract of L. wollei to mussel hemocytes.