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Heat shock proteins (HSP) are highly conserved in their structure and released in case of stress. Increased metallothionein (MT) synthesis is associated with increased capacity for binding heavy metals. Healthy juveniles of grass carp were exposed to sublethal dose (1.495 mg L -1 ) of cadmium for 28 days. Simultaneously, a control group was also run to compare difference of total RNA expression levels in cadmium-treated and control groups. The cadmium levels in the tissues of treated fish recorded were 1.78 ± 0.10 mg L -1 , 1.60 ± 0.04 mg L -1 , and 2.00 ± 0.05 mg L -1 , respectively. Several histological alterations including edema, hemorrhage, dilated sinusoids, hypertrophy, hyperplasia, congestion of central vein, and nuclear alterations were observed in cadmium-exposed fish. Stress gene (metallothionein and heat shock proteins) mRNA transcription levels were studied by mRNA extraction and cDNA preparation by using PCR. The expression level of heat shock protein gene was higher as compared to metallothionein and beta-2-microglobulin gene after cadmium exposure. This study reports various stress-related immune-responsive changes of immune proteins, heat shock proteins, metallothionein, and histopathological changes in fish due to cadmium toxicity that make the fish immunocompromised which may be considered as the biomarkers of cadmium toxicity in other experimental species., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ghazala Jabeen et al.)