Background and aim: Cocaine is recognized for its high toxicity to several vital organs, such as the brain, the liver as well as heart and blood vessels. However, the underlying mechanisms of cocaine-induced toxicity remain insufficiently understood. Heat shock protein 70 (HSP70) is the primary molecular chaperone involved in maintaining protein quality, engaging in various cellular activities through its interaction with diverse client proteins and serves as the main coordinator of the cellular proteostasis system. We aimed to assess serum (HSP70) levels in the present study, and to explore potential associations with selected biochemical markers in individuals with cocaine dependence. Materials and methods: A case-control study was conducted involving 120 Iraqi participants, comprising 60 males diagnosed with cocaine dependence (aged 18–50 years) and 60 healthy males as control group (aged 18–50 years). Serum levels of HSP70 and various metabolic markers including benzoylecgonine, (SOD), (GPx), (TNF-α), (IL-6), (hs-CRP) and D-dimer were measured in all subjects. Statistical analyses were performed to compare the two groups and evaluate correlations among the investigated parameters. Results: The results indicated that the mean level of the biomarker benzoylecgonine was positive in the cocaine addiction group, whereas it was negative in the group of control, with a significant statistically difference (P= 0.02). Statistical evaluation revealed a significantly reduction in (SOD) levels among individuals with cocaine addiction as compared to the control group (97.7±19.4 versus 223±24.7, P=0.03), respectively. A significantly decline in serum (GPx) levels in group of the cocaine addiction relative to the group of control (99.2±10.7 versus 172.5±13.7, P=0.01), respectively. Serum levels of (HSP70) was a significantly increased in individuals with cocaine addiction as compared to the control group (3.6±1.3 versus 1.01±0.46, P=0.02), respectively. Serum levels of D-dimer was a significantly increased in individuals with cocaine addiction as compared to the group of control (750±35 versus 300±20, P=0.03), respectively. HSP70 levels in this findings revealed a strong significant inverse correlations with SOD and GPx, while a strong significant direct correlation with D-dimer.