Investigation of concentrations of organic and inorganic pollutants (hydrocarbons, including oil hydrocarbons, and trace elements – heavy metals and metalloids) in the Ham Luong River in the Mekong Delta was carried out and water quality was assessed by comparing the obtained levels of values with the regulatory limits of concentration. The determination of the total content of hydrocarbons and oil hydrocarbons was made by gas chromatography method; the trace elements were measured by ICP-MS technique after chemical treatment of samples. The content of oil hydrocarbons in the Ham Luong River water ranged from 0.042 to 0.076 mg/l. These values were quite high, exceeding the sanitary standard (0.05 mg/l) for fishery reservoirs, or approaching it, but they were lower compared to Vietnam national standard for domestic supply water (0.1 mg/l). The content of hydrocarbons in suspended matter was in the range of 0.011–0.37 mg/l. The concentrations of 15 trace elements were studied, nine of them (Ni, Fe, V, As, Se, Be, Cd, Sb, Tl) did not exceed any of the established regulatory limits of concentration for surface water. However, concentrations of six trace elements (Pb, Zn, Cu, Co, Ag, Mo) were found to exceed the standard regulatory limits. Among the studied 15 trace elements, critical and potentially critical elements were identified, which are subject to primary monitoring control. Chemoecological studies of water quality are important for monitoring of the ecological and sanitary water state for ensure the quality of consumed natural resources and to preserve the biological diversity of the Mekong Delta ecosystems.