Abstract We evaluated the factors that control the variability in dissolved cadmium (Cdd), phosphate (PO43−) and the Cdd/PO43− ratio in the upper 1000 m of the deep region of the Gulf of Mexico (GoM), a marginal sea where trace element data are limited. These variables were compared to data from studies of adjacent areas (in the Western Central Atlantic), related to physical processes (mesoscale structures and upwelling events) occurring inside the GoM, and to dinoflagellate and diatom abundances in surface waters of this region. Vertical distributions of Cdd concentrations and the Cdd/PO43− ratio displayed the typical nutrient profile that has been extensively reported for different oceans. Cdd and PO43− concentrations in the GoM were higher than those in the Western Central Atlantic. The slope of the Cdd vs. PO43− relationship for samples within the Loop Current (LC) in the GoM was similar (242 pmol μmol−1, R2 = 0.96) to that calculated for the Western Central Atlantic waters (same depth range) that reach the GoM through the LC (235 pmol μmol−1, R2 = 0.98). The linear regression for all the GoM samples, though having a similar slope (249 pmol μmol−1), presented a larger deviation (R2 = 0.91). We propose that this deviation is due to spatial inhomogeneity that can be explained by 1) preferential remineralization of PO43− vs. Cdd at subsurface waters in some regions, 2) Cdd inputs from the north, transported by mesoscale processes, and 3) interactions with the continental slope at the minimum O2 layer. Local changes in the relationship between Cdd and PO43− were traced with Cd*, which represents the deviation of measured Cd to that expected by the deep-water Cdd vs. PO43− relationship. Cd* presented mainly negative values at surface and subsurface waters (~150 m) indicating preferential uptake of Cdd vs. PO43− by the phytoplankton at the surface and preferential remineralization of PO43− vs. Cdd from the organic matter at the subsurface waters. At deeper waters (~400–1000 m) Cdd was preferentially remineralized. In order to understand the inhomogeneity of the horizontal distribution of Cdd, PO43− and the Cdd/PO43− ratio in surface waters, three regions were defined considering their biological and physical characteristics. These were: I) the Oligotrophic region (in the northwest GoM) where the variability in the Cdd/PO43− ratio was largely explained by salinity, II) the Upwelling region (off the coast of the Yucatan Peninsula) where the variability in the Cdd/PO43− ratio was principally due to the diatom abundance and, III) Semi-permanent Cyclonic Gyre region (Bay of Campeche) where the variability in Cdd and the Cdd/PO43− ratio were primarily influenced by the upwelling generated by the cyclonic gyre, and the variability in PO43− was likely due to the consumption of this nutrient by phytoplankton. In summary, physical processes, river inputs, and phytoplankton abundance appear to play an important role in explaining the spatial variation in the Cdd/PO43− ratio.