Amu Darya river, one of the main water resources of Uzbekistan, shows a relevant longitudinal enrichment of soluble contents which strongly limits the human uses of its waters. Because of the low natural run-off processes, salts and pollutants are mainly driven to the river by the return waters used for washing and irrigating the surrounding lands. The influence of return waters on stream quality is dramatically relevant in the lower reaches of the river where almost all the flowing waters have been previously used for the agriculture practises. To provide analytical evidence on the potential effects of return waters on the quality of the Amu Darya river, the paper reports and comments data on salinity and metals contents of the waters flowing in the artificial channel network of Bukhara and in the Amu Darya river, from Bukhara up to the dam forming the Tuyamuyn Hydro Complex (THC). A total of 15 sampling sites were selected for the analytical survey: Two sites were located on the Amu Darya river downstream from the inflow of the return waters from Bukhara, two in the river entering in the THC, and three downstream from the dam forming the reservoir complex. The waters entering and leaving the Bukhara agricultural area were sampled in two main collectors, while the waters flowing in the channel system were sampled in six distinct collectors. The following parameters were considered in the survey: pH, Oxygen, Hardness, Salinity, Conductivity, P-PO4(3-), P tot, N tot, N-NO3(2-), N-NO2-, COD, Ca2+, Mg2+, Fe, Mn, Zn, Cr, Cu, Ni, Cd, Pb. Salt concentrations below 1000 mg/l were measured in the Amu Darya waters upstream to Bukhara. In the drainage system, salinity exceeds the palatability limit and reaches the maximum peak of 3200 mg/l in the outflow collector. Due to dilution effects, salinity returns to lower values (400-700 mg/l) along the Amu Darya river downstream from Bukhara; calcium and magnesium resulted the major constituents of the overall salinity. No serious metal contaminations were detected in the waters entering and leaving the examined channel system. Differently, the Amu Darya waters upstream to the THC showed a relevant metal contamination, with Cr, Ni, Fe concentrations exceeding the limits for human consumption. In the downstream sites, located in the Tuyamuyn Hydro Complex and in the Amu Darya river flowing out from this reservoir, excluding Fe, all the examined metals showed lover concentrations and values below the normative limits. The direct human consumption of the lower Amu Darya waters is strongly limited by salinity and by metal contamination. Although the salinity of the return waters from the Bukhara drainage system results in above normal limits, no corresponding increases were measured in the Amu Darya river downstream from the return water inflow at the time of the survey. As for the metal contamination of the Amu Darya river, the survey revealed the presence of relevant sources of metal contamination downstream from Bukhara external to the agricultural drainage system. This contamination resulted in reduced sedimentation processes taking place in the limnetic zones of the Amu Darya river upstream to the dam forming the Tuyamuyn Hydro Complex. To fully understand the longitudinal increase of Amu Darya salinity, an evaluation of the cumulative effects of the loads from the main agricultural areas is required, also by using mass-balance models. As for the metals, an investigation should be addressed to identify the anthropogenic sources of contaminations present in the lower Amu Darya region and the metal loads should be diverted.