Pb is one of the most extensively used harmful heavy metals in Bangladesh, and its occurrence in waters affects aquatic organisms significantly. The tropical pearl mussel,Lamellidens marginalis,was exposed to different concentrations (T121.93 mgL−1, T243.86 mgL−1, and T387.72 mgL−1) of Pb(NO3)2and was evaluated against a control C 0 mgL−1of Pb(NO3)2, followed by a 96 h acute toxicity test. The LC50value was recorded as 219.32 mgL−1. The physicochemical parameters were documented regularly for each treatment unit. The values of % SGR, shell weight, soft tissue wet weight, and weight gain remained statistically higher for the control group in comparison with the treatment. No mortality was noted for control units, while a gradually decreased survival rate was recorded for the different treatment groups. Fulton’s condition factor was recorded as highest in the control and lowest in the T3unit, while the condition indices did not vary between the control and treatment groups. The hemocyte was accounted as maximum in the control and T1, while minimum in T2and T3. The serum lysosomal parameters also followed a similar pattern, and a significantly low level of lysosomal membrane stability, and serum lysosome activity was noted for T3and T2units in comparison to the control group. The histology of the gill, kidney, and muscle was well structured in the control group, while distinct pathologies were observed in the gill, kidney, and muscle tissue of different treatment groups. The quantitative comparison revealed that the intensity of pathological alteration increased as the dosage of Pb increased. The current study, therefore, indicated that intrusion of Pb(NO3)2in the living medium significantly alters growth performance and hemocyte counts, and chronic toxicity induces histomorphological abnormalities in vital organs.