Exposure to harmful and dangerous factors at ore mining facilities poses health risks to workers that are associated with prolonged exposure to airborne chemicals in the work area. Realized, these risks undermine physical condition of people doing key ore mining jobs underground. Relying on the target protein analysis, this study aimed to assess the job-related harm to the health of ore mining workers resulting from exposure to metals airborne in the work zone. The participants were involved in copper-nickel ores mining. To evaluate the impact of metals from the working zone air on their health, we conducted chemical, proteomic, statistical, and bioinformatic analyses on the collected samples and data. With the mean per-shift exposure to metals of up to 0.2 mg/m³ (up to 4 times the MPC), the blood supernatant concentrations of cobalt, chromium, nickel, copper, and manganese increased by 1.4 to 2.6 times in the study group compared to the control group. Comparison of proteomics datasets revealed 33 significantly different protein spots. In 15 of them, the change in intensity was related to the increased concentration of the considered metals in the supernatant. Identification and analysis of proteins from these spots revealed their association with impairments in the functions of the nervous, cardiovascular, and digestive systems. The identified proteins were involved in the development of oxidative stress, metabolic and neurodegenerative disorders. Proteomic analysis improves the prediction and early prevention of occupational adverse outcomes among the ore mining industry workers.