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Black jaw tilapia (S. melanotheron) collected from Awba Dam (a watershed recipient of effluents from anthropogenic sources) was analysed for biological responses and trace metal burden with the aim of evaluating sex differences in these responses as a measure of environmental and biota health status. Concentration of heavy metals in fish muscle were analysed and showed values above WHO permissible limits for food. Physiological and biochemical responses (AST, ALT, ALP, total protein, albumin, globulin, BUN, Na + , K + and creatinine) showed apparent sex-related differences. Among antioxidant defence system, mt mRNA and proteins showed higher levels in male S. melanotheron. CAT and GPx activities were significantly higher in males than in female fish, while the corresponding mRNA showed an opposite trend with higher transcripts in females than males. Further, while GST activity was apparently higher in females, GR activity was significantly higher in males, compared to female fish. ZnCu-sod mRNA showed significantly higher transcript levels in males, than females. Overall, the trend in these biological responses showed direct relationship with heavy metal concentrations in fish muscle and sediment. These relationships were revealed using PCA that produced significant groupings between physiological, biochemical and oxidative stress variables and muscle/sediment trace element burden. Specifically, the PCA biplots showed that these biological variables were due to the presence of the heavy metals in the dam. Therefore, the sex differences in the measured cellular adaptations of S. melanotheron in relation to the toxic conditions at the dam may have significant consequences on osmotic balance and cellular processes that regulate biochemical/antioxidant responses towards metabolism, behaviour, growth, reproduction and survival of Awba dam resident fish species. Thus, these responses should be compared to a suitable reference site to discern the extent of effects of the Awba Dam biota for monitoring purposes., Competing Interests: Declaration of competing interest There are no conflicts of interest associated with our paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)