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Spatial and seasonal mobilization trends of metals in surface water were evaluated in the US–Mexico San Pedro River (SPR). Water samples were collected at five sampling stations for the analysis of dissolved oxygen, pH, electric conductivity, sulfates, and metals (Cd, Cu, Fe, Mn, Pb, and Zn). Quality of the water was characterized through Ecological Criteria of Water Quality (ECWQ) established in Mexico and Water Quality Criteria (Environmental Protection Agency (EPA)). High total metal concentrations were detected as follows: Fe > Cu > Mn > Zn > Pb > Cd. Metal concentrations were slightly higher in dry season than in rainy season: Cd (below detection limit (BDL)–0.21 mg L
−1
), Cu (BDL–13 mg L
−1
), Fe (0.16–345 mg L
−1
), Mn (0.12–52 mg L
−1
), Pb (BDL–0.48 mg L
−1
), and Zn (0.03–17.8 mg L
−1
). Low pH and dissolved oxygen values as well as high sulfate content were detected in both seasons. High values of metals (Cd, Cu, Fe, Mn, Pb, Zn) were detected at station E1 representing pollution source, as well as at stations E2 (Cd, Cu, Fe, Mn), E3 (Fe, Mn, Pb), and E4 and E5 (Fe, Mn). Detected concentrations exceeded maximum permissible established in ECWQ and Water Quality Criteria (EPA). Efflorescence salts on sediments in the dry season could increase levels of metals in water column. This study provides valuable information on the potential mobility of metals in surface water of SPR located in an arid environment where transport processes are strongly linked to climate. The information derived from this study should help the regional and national authorities to address present environmental regulations.