We analyzed dissolved nutrient, trace metal and vitamin (B-vitamins and methionine) concentrations in the lower course of the Moulouya River (MR, Morocco) and its estuary. The flow of this African river has changed drastically (a reduction of almost 50%) in the last 50 years due to the regulation of the river flow through dams and alterations of the course constructed to satisfy population necessities and growing agricultural requirements. Consequently, it has produced a remarkable increase in nitrate concentrations (up to 270 μM) and alteration of N:P ratios within the river, as well as a reduction of overall P and Si efflux to nearby coastal waters. Despite the historical mining activities in the upper MR, concentrations of Pb, Zn and other metals in sediments and waters do not display significant contamination as compared with other Mediterranean rivers, mainly due to the retention by dams of upstream metal contamination. Mean concentrations of dissolved B-vitamins in the river showed lower levels (13–55% lower) than those in coastal waters and hence the river does not represent an important B-vitamin source.