Metal pollution is one of the most prevalent human pollutants to which mosquito larvae are subjected in agricultural and urban environments. Culex pipiens are rapidly adapted to polluted environments. The present research investigated the impact of exposure of Cx. pipiens larvae to copper chloride (CuCl₂) and cadmium chloride (CdCl₂) on the biochemical, genotoxic, and molecular responses. Various concentrations of CuCl₂ and CdCl₂ were evaluated for toxicity against late third-instar Cx. pipiens larvae. The larvae were treated for 24hr with the LC₅₀ of CuCl₂ and CdCl₂. Copper chloride significantly accumulated in the Cx. pipiens larval tissues compared to CdCl₂. Biochemical studies revealed that these heavy metals increased total protein content, and catalase and peroxidase activities. Glutathione S-transferase, α-esterase, and β-esterase activities were reduced in CuCl₂ treatment while increased in case of CdCl₂ treatment. All parameters of the comet assay, viz., % of damage, tail length, DNA % in the tail, tail moment, and olive tail moment increased with varying levels relative to the control. Gene expression studies demonstrated significant down-regulation of pollution-biomarker genes, acetylcholiesteras (AChE) and cytochrome P450 (CYP450), and significant up-regulation of heat shock protein (HSP), superoxide dismutase (SOD) and metallothionein (MT) genes. In conclusion, Cx. pipiens larvae can be considered an effective bioindicator for heavy metal pollution, facilitating regular studies on metal pollution in aquatic ecosystems.