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Geochemical analysis was carried out on samples of environmental phases (water, sediments, and soils) from La Barra de Santiago estuary (El Salvador, Central America) and adjacent streams to understand the dynamics and possible environmental and health effects of heavy metals, nutrient and sulfate concentrations in the ecosystem. Physiochemical parameters such as nutrient concentration (Nitrate and Phosphate), oxidation reduction potential (ORP), dissolved oxygen (DO), conductivity, total dissolved solids (TDS), pH, temperature, Chloride, Iodide and sulfate concentrations were determined using spectrophotometric methods, while heavy metal analysis was carried out using ICP-MS. Multivariate statistical methods, including correlation analysis (CA) and principal component analysis (PCA) were applied to define the mutual relationships between these parameters. Low concentration of sulfate in the water and sediments suggest it is unlikely that sulfur contamination due to the eruption of Santa Ana volcano in 2005 could be causing the lack of macroinvertebrates in the region. Phosphate in sediments and soil samples has low variability in concentration probably due to buffering by the solubility of phosphate minerals, whereas Nitrate concentration in the sediment is higher than in soil samples. High nutrient concentration and chloride in the region with low DO (symptoms of eutrophication) suggest hypernutrification could be the driver for the lack of macroinvertebrates in the estuary. The statistically significant relationships between Sr, Rb and Cl, and between Sr, Rb and SO4, suggest a chemical contribution from marine sources for these elements, while correlation between Fe, Cu, Cd, Zn, Cr, Ce, Co and Al indicates inland input into the ecosystem for these metals. Lastly, results from sediment quality assessments using several pollution indices such as geoaccumulation index (Igeo), mean-ERM quotient, concentration factor (CF), pollution load index (PLI), and contamination Factor (Cf) shows the presence of high Ni and Cr concentration in the ecosystem which could be responsible for the lack of macroinvertebrates in the estuary. The present study serves as the first insight into the environmental quality assessment of La Barra de Santiago estuary and its adjacent rivers and raises awareness for immediate response towards conservation and protection of this biodiversity rich ecosystem.