This study assesses the water quality of 13 lakes and the Tisa River within the protected area of Tisa River in Romania, focusing on heavy metal contamination and potential human health risks. The research analyzed 20 elements and 16 physico-chemical parameters to evaluate the water's chemical composition and pollution status. The results showed that the water is rich in Ni and Fe, likely due to interactions with groundwater containing these elements. The water is characterized by potential contamination, which could negatively affect human health if consumed directly or through the food chain. Piper and Gibbs plots categorized the water into three types based on water-rock interactions: mixed Ca²⁺-Na⁺-HCO₃⁻, CaCO₃⁻, and Na⁺-HCO₃⁻. Pollution indices, including the Heavy Metal Pollution Index (HPI) and Heavy Metal Evaluation Index (HEI), indicated three pollution categories related to the levels of As, Ni, and Fe. The study found that the chemistry of the lakes and surface waters is influenced by both geogenic and anthropogenic factors. The findings highlight the need for understanding the mechanisms affecting water quality, improving and conserving natural water resources, and identifying potential human health risks. The study also identified that the water quality is generally good, with pH in normal range, adequate electrical conductivity, and high oxygenation. However, some samples showed high concentrations of heavy metals, which could pose health risks. The HPI scores ranged from 11.8 to 129, indicating high pollution levels in some samples, while HEI scores ranged from 0.7 to 28, indicating three pollution levels. The study emphasizes the importance of monitoring and managing water resources to mitigate potential health risks and ensure sustainable use. The research underscores the need for further studies on human health risks associated with heavy metal exposure through water ingestion and contact.This study assesses the water quality of 13 lakes and the Tisa River within the protected area of Tisa River in Romania, focusing on heavy metal contamination and potential human health risks. The research analyzed 20 elements and 16 physico-chemical parameters to evaluate the water's chemical composition and pollution status. The results showed that the water is rich in Ni and Fe, likely due to interactions with groundwater containing these elements. The water is characterized by potential contamination, which could negatively affect human health if consumed directly or through the food chain. Piper and Gibbs plots categorized the water into three types based on water-rock interactions: mixed Ca²⁺-Na⁺-HCO₃⁻, CaCO₃⁻, and Na⁺-HCO₃⁻. Pollution indices, including the Heavy Metal Pollution Index (HPI) and Heavy Metal Evaluation Index (HEI), indicated three pollution categories related to the levels of As, Ni, and Fe. The study found that the chemistry of the lakes and surface waters is influenced by both geogenic and anthropogenic factors. The findings highlight the need for understanding the mechanisms affecting water quality, improving and conserving natural water resources, and identifying potential human health risks. The study also identified that the water quality is generally good, with pH in normal range, adequate electrical conductivity, and high oxygenation. However, some samples showed high concentrations of heavy metals, which could pose health risks. The HPI scores ranged from 11.8 to 129, indicating high pollution levels in some samples, while HEI scores ranged from 0.7 to 28, indicating three pollution levels. The study emphasizes the importance of monitoring and managing water resources to mitigate potential health risks and ensure sustainable use. The research underscores the need for further studies on human health risks associated with heavy metal exposure through water ingestion and contact.